Taking nutritional supplements is common among multiple myeloma patients and other cancer patients. These supplements, including vitamins, minerals, and various plant compounds, may be important to keep the body healthy, aid in the treatment of myeloma, or to reduce negative side effects of treatment.

However, supplements, even those found naturally in foods, have the potential to interact poorly with chemotherapy or other treatments. Physicians typically agree that eating a balanced and nutritional diet is important, but they are often hesitant to recommend the use of certain supplements, since there may be little to no research to show that they are effective and safe in myeloma patients (see a related Beacon forum discussion). So, please discuss all supplements with your doctor before taking any.

If you and your doctor decide that certain supplements may be right for you, there are several important things to keep in mind. In general, supplements should be taken with food, unless otherwise indicated. If you are being treated with Velcade (bortezomib), avoid taking supplements on the days you receive Velcade, as they can diminish the efficacy of Velcade. If your doctor approves a supplement regimen, ask your doctor to provide specific instructions on when and how to take the supplements.

In order to help you decide which supplements you may want to discuss with your doctor, this article will provide for each nutrient: information on its potential purpose in multiple myeloma treatment, where to find it in your normal diet, and the suggested doses for myeloma patients.

Acetyl-L Carnitine

Some small studies suggest supplementing with acetyl-L carnitine, a nutrient normally made in sufficient amounts by the body, can help reduce the symptoms of peripheral neuropathy (nerve damage to arms and legs that is a common side effect of myeloma treatment). Acetyl-L carnitine may also protect heart cells from damage from Doxil (doxorubicin liposomal) treatment.

Acetyl-L carnitine is found in beef, pork, and milk. As a supplement for peripheral neuropathy, patients can try 500 milligrams twice a day with food. Up to 2 grams a day is safe, but over 5 grams a day can cause diarrhea, appetite changes, body odor, and rash.

Alpha Lipoic Acid

Alpha lipoic acid is an antioxidant that is commonly used in supportive therapy for peripheral neuropathy in people treated for multiple myeloma. It is an antioxidant that is normally made in the body, but people can also take extra alpha lipoic acid through supplements. Myeloma patients with peripheral neuropathy can take 300 milligrams to 1 gram daily, with 600 milligrams often recommended for up to four weeks.

Patients should be aware that one study done in myeloma cells in a lab found that alpha lipoic acid may reduce the effectiveness of Velcade treatment.

Calcium

People with multiple myeloma may take calcium along with vitamin D to help support their bones. However, bone breakdown during multiple myeloma also releases unhealthy amounts of calcium in the blood, so patients should consult their doctors before considering calcium supplements.

Curcumin

Curcumin, a compound found in the spice turmeric, may work to kill myeloma cells and prevent them from multiplying. For those who have the pre-cancer conditions monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma, curcumin may slow progression to active multiple myeloma, but this has not yet been supported by clinical research.

At the same time, patients should beware that curcumin can also suppress the immune system, which can be dangerous for people with multiple myeloma, smoldering multiple myeloma, or MGUS. For more information, please see the related Beacon news and discussion.

There is no standard established dose for curcumin in multiple myeloma. In the few small studies available on curcumin as a myeloma therapy, patients usually take about 4 grams daily spread out over many doses throughout the day. In India, where turmeric is popular in cooking, the average daily consumption is much less—60 milligrams to 200 milligrams through diet.

Enzymes

A mixture of the enzymes papain, trypsin, and chymotrypsin may weaken myeloma cells and increase the likelihood of responding to conventional chemotherapy. Anecdotal evidence suggests drinking papaya juice, which is rich in papain, may also be helpful in cancer therapy (see related Beacon news).

Eating papaya or drinking papaya juice generally poses little risk, though people who are pregnant, are allergic to kiwi fruits or figs, or have problems with blood clotting should avoid papain. Also, raw papain can irritate the skin.

There is little data on the effectiveness of this type of therapy or how much enzyme supplement to take for multiple myeloma. An ongoing Phase 3 trial is studying three daily doses of a product called Wobe Mugos E, which contains 100 milligrams of papain, 40 milligrams of trypsin, and 40 milligrams of chymotrypsin. Side effects of papain supplements, such as Wobe Mugos E, include throat and stomach irritation.

Fish Oils

Fish oils commonly contain plenty of omega-3 fatty acids, which may boost peripheral nerve health. For this reason doctors sometimes recommend them for peripheral neuropathy. Omega-3 fatty acids may also work against cancers by reducing inflammation.

Omega-3 fatty acids perform many important functions in the body and are an essential part of a healthy diet. Healthy patients are recommended to take 1.1 grams of omega-3 fatty acids a day for women and 1.6 grams a day for men. No recommendations specifically for myeloma patients were found. Patients should be careful not to take more than 3 grams a day without medical supervision because of an increased risk of bleeding.

The science on the effects of omega-3 fatty acids on multiple myeloma is still preliminary—two studies from the 1990s showed certain omega-3s kill myeloma cells in mice. For those interested in trying fish oils in a clinical trial, a trial is recruiting volunteers who have MGUS or smoldering multiple myeloma for a study on whether omega-3 supplements will delay or prevent the progression of these diseases to symptomatic multiple myeloma. The trial is starting patients on 1.25 milligrams three times a day, and the dosage will be increased for patients who can tolerate it.

Ginger

Ginger is a well-known home therapy for nausea. The latest science supports using ginger alongside prescribed nausea medication to reduce nausea from chemotherapy (see related Beacon news). The study showed that 0.5 gram to 1 gram of ginger daily for three days before chemotherapy and the first three days of chemotherapy significantly reduced nausea.

Glutamine

Supplements of the amino acid glutamine may help with several major side effects of high dose-chemotherapy and bone marrow transplantation. Small studies have shown it may reduce peripheral neuropathy, mouth sores and mouth ulcers, and infections.

Patients can take 15 grams of a pure L-glutamine powder twice daily for a total of 30 grams.

Green Tea

A compound found in green tea, called epigallocatechin-3-gallate (EGCG), may aid in killing myeloma cells and prevent myeloma cells from multiplying. However, it may also block the anti-cancer activity of Velcade, leading researchers to advise people with multiple myeloma undergoing Velcade therapy to avoid green tea products and EGCG supplements (see related Beacon news).

For people with MGUS or smoldering multiple myeloma, the compounds in green tea may slow down or prevent their pre-cancer conditions from progressing to multiple myeloma. Since most MGUS and smoldering myeloma patients are not actively treated, there is no worry of interference with chemotherapy. One Phase 2 clinical trial is studying the effects of a daily green tea extract on people with MGUS and smoldering myeloma. The trial is recruiting participants in Detroit.

Iron

Anemia (low red blood cell counts) is a symptom of multiple myeloma and is also a common side effect of many myeloma treatments. Iron supplements may help certain people with their anemia. Anemia is often treated with a prescription hormone called erythropoietin that stimulates red blood cell production. In severe cases, blood transfusions may be necessary.

For those whose anemia therapy would get a boost from iron, doctors may recommend an oral iron supplement or, if that is not enough, intravenous iron. In addition, patients can try including iron-rich foods in their diet such as dried beans, fortified cereal, beef, and eggs.

At the same time, people with multiple myeloma who get blood transfusions are at risk for having too much iron in their bodies, so iron supplements are not right for all myeloma patients. Doctors can tell patients how much iron is needed, depending on their condition.

Magnesium

Magnesium may help with peripheral neuropathy. It also helps regulate calcium levels and can help strengthen bone. Green leafy vegetables, almonds, cashews, and halibut are all good sources of this essential mineral.

People with multiple myeloma can also take 250 milligrams of magnesium twice daily through an over-the-counter supplement, or they might get a prescription for a daily 400-milligram supplement, depending on how much magnesium their doctors find in blood tests. Patients should beware that too much magnesium can cause diarrhea.

Potassium

Doctors may recommend potassium for people getting treated for multiple myeloma to help with peripheral neuropathy. Patients can get potassium from food sources such as sweet potatoes, bananas, citrus fruits, peas, red meat, and chicken, or their doctor may recommend potassium supplements.

There are no documented cases of people getting too much potassium from food, but supplements can cause hyperkalemia, a dangerous condition than can lead to sudden cardiac arrest. Since the kidneys work to remove extra potassium from the body, people with multiple myeloma, which often reduces kidney function, might be especially vulnerable. Multiple myeloma patients should be especially careful to take potassium supplements only under direction from their doctors.

Resveratrol

Resveratrol, a compound abundant in grape skins, may kill myeloma cells, prevent myeloma cells from multiplying, and enhance the effects of some common chemotherapy drugs (see related Beacon news).

Those interested in including more resveratrol in their diet can enjoy grapes, purple grape juice, red wine, peanuts, blueberries, and cranberries.

There are also many resveratrol supplements available on the market. However, because there have not been any completed clinical trials on resveratrol in multiple myeloma therapy, there is no established dosage. A Phase 2 clinical trial was studying the effects of 5 grams daily of a formulation of resveratrol in multiple myeloma patients. However, the trial was suspended earlier this year after several patients developed kidney failure (see related Beacon news).

Vitamin B

B vitamins, including vitamin B-1 (thiamine), vitamin B-2 (riboflavin), vitamin B-6, vitamin B-12, and folic acid, are important for the formation of red blood cells, enhance the immune and nervous systems, and more. People with multiple myeloma often have low red blood cells counts and can suffer from peripheral neuropathy, so getting enough B vitamins may be especially important for those with multiple myeloma.

Good food sources of B vitamins include fortified breakfast cereal; other fortified grain products; animal products such as fish, poultry, meat, and dairy; vegetables such as carrots, peas, and leafy greens; fruits such as avocadoes, grapes, and dates; and beans.

Vitamin B-1 and vitamin B-12 are so common in foods, people rarely need to take supplements for them. For the other B vitamins, supplements commonly come in a B-vitamin complex formula that includes many or all of the B vitamins in one pill.

Recommended amounts for multiple myeloma patients with peripheral neuropathy include 50 milligrams of vitamin B-6 daily (but not more than 100 milligrams a day) and 1 gram of folic acid daily.

Vitamin C

As an antioxidant, vitamin C helps protect cells from environmental damage that may lead to cancer. It also functions in protecting the immune system. The best protective benefits seem to result from obtaining vitamin C through fruits and vegetables, but the vitamin is still one of the most popular supplements for people with cancer.

Myeloma patients who are interested in vitamin C supplements should be aware that taking antioxidants on the same day as Velcade treatment reduces Velcade’s therapeutic effects (see related Beacon news). However, patients can still enjoy fruits and vegetables that are naturally high in vitamin C, such as red peppers, citrus fruits, kiwi, and broccoli.

Vitamin D

Vitamin D works with calcium to build bone, and recent research suggests it might be important in reducing some signs and symptoms of multiple myeloma. Supplements may help people with multiple myeloma deal with chronic bone pain, weakness, fatigue, and peripheral neuropathy. Meanwhile, vitamin D deficiency may be associated with poorer multiple myeloma prognoses (see related Beacon news).

Patients should aim to get 800 international units (IU) to 1,200 IU of vitamin D daily. Getting out in the sun every day for 15 minutes can go a long way toward keeping vitamin D levels up. Including fortified cereal and fortified milk, cheese, and other milk products in the diet can also prove beneficial. For those who cannot eat or drink dairy products, most alternatives, such as soy milk, rice milk, and almond milk, are fortified as much as cow’s milk. Vitamin D is also present naturally in fatty fish, such as salmon or tuna.

Many people do not get enough vitamin D through sun exposure and their diet, however. A daily supplement with 400 IU to 800 IU of vitamin D2 (ergocalciferol) or D3 (cholecalciferol) can help.

Vitamin E

For those suffering from peripheral neuropathy, vitamin E supplements may help. This antioxidant vitamin may protect nerves during therapy, especially with Velcade or thalidomide.

Additionally, Vitamin E may help heal mouth sores caused by chemotherapy. In a 2003 entry, multiple myeloma blogger Jon Siegel wrote about applying the contents of a vitamin E capsule to his mouth sores. He found he had “a relatively easy time of it compared to other folks” who had gone through chemotherapy.

For food sources of vitamin E, look to almonds, sunflower seeds and oil, peanut butter, and safflower oil. If taking a supplement, 400 IU daily is recommended.

For more information about nutrition for myeloma patients, see Part 1 in the series.  Feel free to post as a comment any recommendations your physicians made about these or additional supplements, and please remember to always consult with your doctors before taking any new supplements.

Healthy eating can help people with multiple myeloma heal faster, feel more energetic, respond better to treatment, and protect a vulnerable immune system. But treatments like chemotherapy and stem cell transplants can sap appetites, leading to malnutrition and vitamin deficiencies.

However, as a multiple myeloma patient, you can manage your nutrition by following the principles of a balanced diet that you are probably already familiar with, such as eating plenty of colorful fruits and vegetables, getting enough protein, avoiding fried foods, and getting unsaturated fats from sources like fish, nuts, and seeds. You can also meet with a registered dietician during treatment, who will work with you to choose a diet that will help you feel the best you can.

Eating well and getting regular exercise are good ways to prepare for treatment. Once treatment starts, there are many strategies you can use to make up for nutritional deficiencies and to overcome side effects that reduce your appetite.

Strategies For Eating Well During Treatment

“The biggest problem I encounter with myeloma patients is poor intake of protein and calories due to effects of disease progression and treatment,” wrote a University of Arkansas cancer center dietician on the university’s Myeloma Institute website.

Eating snacks and frequent small meals every two or three hours can help increase calorie and protein intake. If you find that you need to gain weight, try adding grated cheese on top of meals, adding powdered milk to cream soups and casseroles, choosing the full-fat versions of dairy products and dressings, or supplementing your diet with nutritional drinks and shakes.

Nausea and vomiting are common side effects of chemotherapy. If you are feeling nauseous, try eating small meals, avoiding strong smells, and eating cold instead of hot foods. Bland, dry foods like crackers and toast and clear liquids like broths, juices, and water may be appealing.

Some treatments can cause sore throats or mouths, or reduced saliva and a dry mouth. Soft, bland foods can help. Soups, milk, pudding, and ice cream are good examples. Avoiding spicy, salty, or tart foods like citrus fruits and avoiding alcohol can also help. Dry and sore mouths are prone to cavities and infections, your doctor may recommend a rinse or brushing after meals to keep your mouth clean.

Another common side effect after stem cell transplantation is an altered sense of taste or smell. Try rinsing your mouth before eating, using different herbs and spices, or adding more salt or sugar to your food. If you do not have a sore throat or mouth, you can try tart, citrus flavors. If you are bothered by a metallic taste in your mouth, try sucking on sugar-free lemon drops or mints and using plastic utensils at meals (see a related Beacon forum discussion for more tips).

Even side effects such as diarrhea, constipation, and fatigue can be managed in part by diet.

Avoiding Infections

In addition to getting enough nutrition, people undergoing multiple myeloma treatment will also need to eat well to help protect their weakened immune systems.

“Decreased red blood cell and white blood cell counts are common side effects of chemotherapy. While patients are aware of this, they often overlook the fact that poor nutrition can also play a role,” wrote the University of Arkansas dietician.

If you have low white blood cell counts, avoid raw foods such as raw seafood, salads, and soft cheeses like Brie or Camembert. Wash your hands often and keep your kitchen especially clean. Doctors or nurses can provide advice on how to keep the home safe while you are vulnerable to infection.

Vitamin Supplements

You may become interested in taking supplements during your myeloma treatment, especially as more studies emerge showing the importance of different vitamins to cancer healing. A few recent studies have suggested that fixing vitamin D deficiency in people with multiple myeloma may lead to better prognoses, and that vitamin D supplementation can reduce bone complications and correct hypercalcemia.

However, excesses of vitamins may interfere with cancer therapies. In particular, vitamin C, green tea, and other antioxidants may interfere with Velcade (bortezomib). In addition, taking more than 100 percent of the recommended daily value of any given vitamin may increase cancer risk. Patients should always consult their doctors before making any changes to their diet, including taking supplements.

Eating well during multiple myeloma and its treatment takes care and planning, but provides patients with an effective, actionable way to feel healthier and respond better to therapy.

For more information, see articles on nutrition by the Leukaemia Foundation (pdf) and the American Cancer Society. Also check out Part 2 of the Beacon nutrition series.

The results of the article, which was published in the journal Cancer Treatment Review, confirm that people with smoldering multiple myeloma may be able to hold off treatment until a later stage in their myeloma.

“The standard of care for patients with smoldering multiple myeloma remains observation until additional randomized trials are completed and show a real benefit,” said Dr. S. Vincent Rajkumar of the Mayo Clinic. Dr. Rajkumar was not one of the study investigators. “The rationale for continued observation is that we do not know if early therapy prolongs survival. However, early therapy has clear risks of toxicity.”

The researchers analyzed results from Phase 3 trials comparing early and late cancer treatment. The scientists found three trials on multiple myeloma, which were published in 1993, 1994, and 2000. In all three studies, patients received non-aggressive treatment with melphalan (Alkeran) and prednisone.

The three trials included a total of 262 people with smoldering multiple myeloma who were at high risk of progressing to multiple myeloma. In each trial, about half of the study participants received treatment as soon as they were diagnosed, and half of the study participants received treatment when they began showing myeloma symptoms.

According to Dr. Rajkumar, treatment should be started as soon as there is any evidence of kidney dysfunction, anemia (low red blood cell counts), bone lesions, or high calcium levels in the blood that are caused by the myeloma.

The researchers were not able to find exactly how many days treatment can be delayed without affecting survival times. They also cautioned that some effects of cancer, such as kidney failure, are life-threatening and need to be treated right away.

These results reinforce that there is a “window of opportunity” after an early smoldering multiple myeloma diagnosis. Patients may be able to choose to wait to start chemotherapy after an important event, like a wedding or a graduation, or after they finish a work task or manage insurance tasks. Younger patients who wish to have children may be able to set aside eggs or sperm.

The research review found similar results for chronic lymphocytic leukemia, lung cancer, and follicular lymphoma. However, it found longer survival times with early treatment for prostate cancer.

“More such studies on a larger scale are needed,” said Dr. Rajkumar. “Such a study will open later in the year in the United States. It is an Eastern Cooperative Oncology Group trial of Revlimid (lenalidomide) versus observation for high-risk smoldering multiple myeloma. Until studies show survival benefits, the standard of care remains observation.”

For more information, please see the article in the journal Cancer Treatment Reviews.

For those with multiple myeloma, this increased risk of osteoporosis means higher risk of fractures even in places in the bone that do not have cancerous cells. For those with monoclonal gammopathy of undetermined significance (MGUS), a blood disorder characterized by a high level of monoclonal protein, or those with smoldering multiple myeloma, their disease-caused osteoporosis may be an early sign of progression to cancer. Bisphosphonate therapy may help, but it has its limitations. (Smoldering myeloma is also known as asymptomatic myeloma or indolent myeloma.)

Osteolytic lesions, or small areas of bone damage, are already a well-known symptom of multiple myeloma. This review found that several studies show that people with multiple myeloma also have general loss of bone density. Women and people with IgA-type multiple myeloma are more often affected.

This loss of bone density can lead to fractures in healthy bone that does not have cancerous cells. One study of 165 people with multiple myeloma found that myeloma patients are nine times more likely to experience bone fractures than the general population. One-third of those fractures occurred in places in the bone that did not have myeloma cells.

People with MGUS also show bone density loss and bone fractures. MGUS is a precursor condition to multiple myeloma in which patients do not have osteolytic lesions or other myeloma symptoms. However, the review covered research that shows people with MGUS may still be at an increased risk for osteoporosis.

In one study of 65 women with MGUS, 35 of the study participants had osteopenia, or bone density loss that is not as severe as osteoporosis, and 17 had osteoporosis. More than half of the study participants had at least one fracture in the spine, compared to less than a quarter of post-menopausal women who do not have MGUS.

Another study of 488 men and women with MGUS found that compared to the general population, the study participants were 2.7 times more likely to experience a fracture in the spine. Older participants, participants who had MGUS longer, and participants who had taken corticosteroid drugs such as prednisone were at the greater risk for fractures.

Bone loss in MGUS may be an early sign of progression to multiple myeloma, the review found. It cited a study of 87 people with MGUS where bone breakdown was “significantly associated” with progression to multiple myeloma. However, it may be difficult to use this information to develop prognoses for patients, because it is not easy to see the breakdown in small bone biopsy samples.

To treat bone problems in multiple myeloma, doctors use bisphosphonate drugs, which decrease bone breakdown, osteolytic fractures, and bone pain. The review found that bisphosphonate therapy may also help increase bone mass and prevent fractures in people with MGUS. In smoldering multiple myeloma, another multiple myeloma precondition that is more advanced than MGUS, bisphosphonate therapy reduced the number of bone fractures in study participants.

However, the treatment did not reduce the amount of abnormal protein or plasma cells in people with smoldering multiple myeloma. Bisphosphonate treatment also did not help prolong or prevent the progression to multiple myeloma in people with either MGUS or smoldering multiple myeloma.

New research is increasingly linking multiple myeloma and its precursor conditions to general bone loss and fractures. This new information may impact how prognoses are developed and how precursor conditions are treated. The scientists who published this new review suggested that researchers further study what factors contribute to bone loss and how bone loss might be used to predict who will develop multiple myeloma from a precursor condition.

For more information, please see the related article in Joint Bone Spine (abstract).

Description

Dacetuzumab is a monoclonal antibody that specifically binds to and works against a molecule called a CD40 receptor, which appears in abnormally high amounts in multiple myeloma cells, as well as in the cells of other blood cancers such as non-Hodgkin’s lymphoma. When dacetuzumab binds to CD40 receptors in a myeloma cell, the cell dies and does not multiply.

Mechanism of Action

Dacetuzumab kills myeloma cells by recruiting the body’s immune cells in two mechanisms, antibody-dependent cellular cytotoxicity and antibody-dependent cellular phagocytosis. It also acts in direct signal transduction, releasing chemical signals into the myeloma cell it binds to that tell the cell to die.

History

Though dacetuzumab is still in its early stages of clinical study, the idea for its action is older. Over the past decade, scientists have been interested in targeting CD40 for cancer therapy because of its abundance in the cells of certain blood cancers, and because it appears to be involved in cell growth.

In 2004, Seattle Genetics, in collaboration with Genentech, began a Phase 1 study of dacetuzumab’s safety and effectiveness in relapsed and refractory multiple myeloma. The results were published in February in the journal Haematologica (pdf). Seattle Genetics now has two more Phase 1 trials underway, studying dacetuzumab with Velcade (bortezomib) and Revlimid (lenalidomide).

Usage in Multiple Myeloma

Dacetuzumab is in Phase 1 testing for multiple myeloma. The two trials that are now underway both study the drug as a treatment for people with relapsed or refractory multiple myeloma; study participants must have tried at least one previous treatment. The two current trials also both study dacetuzumab in combination with another drug, either Velcade or Revlimid. A previous lab experiment, published in the journal Cancer Research in 2005, showed that dacetuzumab may work especially well with Revlimid.

Dosage & Administration

Because dacetuzumab is still under study, no optimal dosages have been established yet. Clinical trials have tested different dosages.

Seattle Genetic Inc.’s first clinical trial of dacetuzumab studied varying weekly doses of the drug, ranging up to 16 mg/kg. The study participants received the drug intravenously. Those who were taking higher doses also took a steroid to reduce the risk of cytokine release syndrome, a side effect of antibody treatments like dacetuzumab.

In one current ongoing trial, study participants receive dacetuzumab intravenously in doses ranging from 2 mg/kg to 12 mg/kg for eight 28-day cycles of treatment, taking fewer doses in later cycles. They receive dacetuzumab on Days 1, 4, 8, 15 and 22 of Cycle 1; then on Days 1, 8, 15 and 22 of Cycles 2 through 4; then just Days 1, 8 and 15 during Cycles 5 through 8. At the same time, they take up to 25 mg of Revlimid daily and 40 mg of dexamethasone (Decadron) weekly.

In the other ongoing dacetuzumab trial, study participants take increasing intravenous doses of both dacetuzumab and Velcade. The ClinicalTrials.gov description of this trial does not give any specific doses.

Side Effects

When used in combination with Revlimid and dexamethasone, the most common harmful effects were mild to moderate fatigue, low white blood cell counts, diarrhea, constipation, and headache. Less than 6 percent of patients stopped treatment because of their side effects. One patient developed a painful viral skin rash called herpes zoster and another developed kidney failure and needed dialysis.

When used alone, the most common side effects were fatigue, headache, nausea and anemia. Most participants had mild to moderate side effects, though 30 percent had more severe ones. Treatment was discontinued by 14 percent of patients because of their side effects and by 11 percent because their myeloma progressed.

Drug Interactions

No drug interactions have been reported at this time.

Precautions

No precautions have been reported at this time.

Ongoing Clinical Trials

Closed
Phase 1:

• Seattle Genetics Inc., Genentech: Study of Dacetuzumab in Patients with Refractory or Recurrent Multiple Myeloma (NCT00079716)
• Seattle Genetics Inc., Genentech: Study of Dacetuzumab, Revlimid, and Dexamethasone in Patients With Multiple Myeloma (NCT00525447)

For a more detailed listing of clinical trials involving dacetuzumab, please check the U.S. government’s clinical trials Web site.

Clinical Trial Results

Dacetuzumab, Revlimid, and Weekly Dexamethasone in Relapsed or Refractory Multiple Myeloma: Multiple Responses Observed in a Phase 1b Study (2009): Among 33 people with relapsed or refractory multiple myeloma, 12 achieved partial response and one achieved complete response after treatment with dacetuzumab, Revlimid, and dexamethasone. The other study participants had stable disease (10 participants), minimal response (4 participants), or progressive disease (2 participants). Scientists were unable to evaluate four participants’ responses and have yet to evaluate the response of three more participants. For more information on this ongoing clinical trial, please see the related American Society of Hematology Annual Meeting abstract.

A Phase 1 Multidose Study of Dacetuzumab in Patients with Multiple Myeloma (February 2010): After treatment with varying doses of dacetuzumab alone, nine out of 44 study participants reached the study’s best response—stable disease. This study helped established the safety of dacetuzumab, allowing the current dacetuzumab clinical trials to move forward. For more information, please see the full study published in Haematologica.

Patient Assistance Programs

Chronic Disease Fund, Inc.
877-968-7233
www.cdfund.org

HealthWell Foundation
800-675-8416
www.healthwellfoundation.com

Links of Interest

Seattle Genetics Inc.’s List of Published Research on Dacetuzumab
http://www.seagen.com/product_pipeline_scientific_publications.shtml#SGN-40

How Monoclonal Antibody Treatments for Cancer Work, by the Mayo Clinic
http://www.mayoclinic.com/health/monoclonal-antibody/CA00082

“The message of the paper is that age-adjusted [risk of developing] myeloma has been stable over 56 years.” wrote Dr. Ingemar Turesson, the study’s lead scientist, in an e-mail to The Myeloma Beacon. “My belief is that earlier reports on increasing (age-adjusted) [risk] of myeloma is explained by better access to health care in older individuals, better awareness of the diagnosis, etc.” His study and a similar one conducted in Olmsted County, Minnesota, support his ideas, he added.

Increasing multiple myeloma rates over time may suggest that environmental factors contribute to the development of multiple myeloma. The longer people are exposed to these factors, the more likely they are to get sick.

However, this new study joins a few others in finding stable multiple myeloma rates, which do not support the idea that environmental factors play a role in the diagnosis of multiple myeloma.

The study also provides evidence against some cancer centers’ anecdotal reports that they have seen increased numbers of younger myeloma patients. These reports are “mentioned and discussed in various contexts, such as scientific meetings, but not really published as far as I know,” wrote Dr. Turesson.

“I found no increase of [risk] in any age group,” he noted. But he also stated that there were so few Malmo residents under 50 years old who had multiple myeloma that his study cannot definitively say if there have been any changes in myeloma rates among them.

To calculate multiple myeloma rates, researchers often rely on data from central cancer registries. The Swedish researchers pointed out that information from central cancer registries may be biased due to progressive diagnostic tools, variations in data reporting, and differences in health care access.

To overcome these potential biases, the Swedish researchers suggested collecting data in a defined population with unrestricted access to health care and reviewing individual patient records to ensure the consistent use of diagnostic tools.

For their study, which they described as the “the longest and largest” on rates of multiple myeloma in a defined population, the scientists searched hospital records, the Swedish Cancer Registry and autopsy registries in the city of Malmo, Sweden, to identify all the city’s residents who had been diagnosed with multiple myeloma between 1950 and 2005.

They examined each multiple myeloma patient’s medical records to determine the patient’s sex, age, and how his myeloma diagnosis was made. They used city census data to calculate multiple myeloma rates for different age ranges.

Overall, they analyzed the medical records of 773 Malmo residents with multiple myeloma, out of Malmo’s total population, which was 190,000 in 1950 and increased to 270,000 by 2005.

The researchers found that the rate of multiple myeloma diagnoses—the number of people diagnosed with multiple myeloma per 100,000 people—has stayed the same since 1950.

They also found that the median age at diagnosis increased from 70 to 74 years and that the share of people with multiple myeloma over 80 years also went up from 16 percent to 31 percent during the 50-year observation period.

These results point to the need for less intense therapies, the Malmo University Hospital researchers concluded in their paper. Older people with multiple myeloma often cannot tolerate intense myeloma treatments such as stem cell transplants.

The steady myeloma rates in their study suggest that major environmental changes in recent years do not seem to affect multiple myeloma, the researchers concluded. That conclusion is indirect, Dr. Turesson added in his e-mail, since his team’s research was not designed to specifically look for environmental factors’ effects on myeloma rates.

The researchers pointed out that their study had some limitations. They could not completely rule out that improvements in diagnosis since 1950 may have affected their results. Secondly, they did not have data available about moves into and out of Malmo during the research period. They added that their results may only apply to white populations and may not be applicable to other ethnicities or countries.

For more information, please see the study in the journal Mayo Clinic Proceedings (abstract).

People with smoldering multiple myeloma have abnormal levels of certain cells and proteins in their blood, but don’t feel the symptoms of multiple myeloma. They are at risk for getting the cancer later.

The amount of plasma cells in a patient’s bone marrow and the amount of M protein in a patient’s blood, or serum, are already used in determining prognoses for people with smoldering myeloma. However, PCLI may provide a finer-tuned prognosis, especially for people with a medium-risk prognosis according to their bone marrow plasma cell and M protein amounts.

“The PCLI measures the proliferative rate of the malignant bone marrow plasma cells,” wrote lead investigator Dr. Madan in an email to The Beacon. “It provides a useful measure of how active the disease is and how it will behave in the near future. It can show a change before the M-protein or percent plasma cell changes.”

Those with a PCLI greater than one percent have a poorer prognosis than those who have a PCLI less than one percent. In their letter to the editor, Dr. Madan and his colleagues at the Mayo Clinic wrote about a study they conducted that shows that PCLI may work in the same way in smoldering myeloma prognoses, too.

The researchers looked at 161 people who were diagnosed with smoldering multiple myeloma and received a plasma cell labeling test. The scientists divided their patients into three groups based on the patients’ bone marrow plasma cell and M protein amounts. For these two measures, greater numbers correspond to poorer prognoses.

The researchers found that for patients with more than 10 percent bone marrow plasma cells but less than 3 g/dL serum M protein, 83 patients out of the 161 studied, having a PCLI greater than one was associated with progressing to multiple myeloma. Two years after their smoldering myeloma was diagnosed, 75 percent of patients with PCLI greater than one progressed to multiple myeloma, compared to 21 percent of patients with PCLI less than one. After five years, all of the patients with PCLI greater than one had multiple myeloma, compared to less than half of patients with PCLI less than one.

For people with both bone marrow plasma cells greater than 10 percent and serum M protein greater than 3 g/dL—the poorest prognostic numbers—there wasn’t a statistically significant difference between those with a PCLI greater than one and those with a PCLI less than one. Among the least at-risk smoldering myeloma patients, who had less than 10 percent bone marrow plasma cells and greater than 3 g/dL serum M protein, all had PCLI less than one, so researchers were not able to make any comparisons.

PCLI is a useful risk factor for people with smoldering multiple myeloma, concluded the researchers’ letter to the editor. In addition, Dr. Madan wrote that “Smoldering multiple myeloma patients with a PCLI of 1 or greater should be followed more closely with frequent follow up visits and lab tests to ensure the timely institution of effective therapy before end organ damage develops.” Researchers can also use PCLI to design more specific clinical trials.

The main drawback to PCLI is that it isn’t widely available, the researchers added. To explain this, Dr. Madan pointed to a lack of awareness, the fact that multiple myeloma is a rare disease in most institutions, the narrow use of PCLI instruments, and the cumbersome process of bone marrow incubation.

The researchers suggested scientists study other tests that, like PCLI, measure the rate at which cancerous plasma cells are spreading. This rate may be key to yielding more specific diagnoses for people with smoldering multiple myeloma.

For more information, please see the letter to the editor in Mayo Clinic Proceedings.

In multiple myeloma and the precursor condition monoclonal gammopathy of undetermined significance (MGUS), cell culture studies and one animal study have shown that curcumin can kill cancer cells and prevent them from multiplying. The Beacon also found two early-stage clinical trials studying curcumin’s effects in people with multiple myeloma and MGUS.  Their results were promising, but not definitive.

All of the studies discussed here suggest that curcumin is relatively safe. In India, where turmeric is used extensively in cooking, the average person consumes 60 to 200 mg of curcumin through his daily diet, according to the National Institutes of Health’s Medline Plus.

Studies in myeloma cells and in mice

Several recent lab studies have demonstrated that curcumin kills myeloma cells and increases the effects of conventional drug therapy:

• At Zhongnan Hospital of Wuhan University in Wuhan, China, scientists found that the addition of curcumin to melphalan (Alkeran) reduced myeloma cell proliferation, increased myeloma cell death, and increased the concentration of melphalan in cells. They found that curcumin reduces the production of a protein that helps tumor cells repair damaged DNA. The journal Annals of Hematology (abstract) published their research in September.
• M. D. Anderson Cancer Center scientists in Houston found that curcumin slowed down the growth of multiple myeloma cells that are resistant to dexamethasone (Decadron), doxorubicin (Adriamycin), and melphalan. It also enhanced the effects of thalidomide (Thalomid) and Velcade (bortezomib). By performing experiments on mice, the researchers confirmed curcumin’s ability to augment the effect of Velcade. They published their findings in the journal Molecular Cancer Therapeutics (abstract) in April.
• Two older studies by the same M. D. Anderson researchers also found evidence of curcumin’s ability to kill myeloma cells, reduce or prevent myeloma cell proliferation, and enhance the effectiveness of conventional drugs. These studies appeared in the journals Blood and The Journal of Immunology (PDF) in 2003.

Clinical trials

Clinical trials on curcumin’s effects on people with multiple myeloma or MGUS have also been promising, but thus far the evidence is limited to small, preliminary studies. The Myeloma Beacon found two such studies.

• In Sydney, Australia, one trial examined 26 people with MGUS who either took 4 g of curcumin by mouth every day for three months, then switched to a placebo, or took the placebo first for three months, then switched to the curcumin treatment. The researchers found that during the placebo phase, study participants’ abnormal protein levels either stayed steady or increased, while during the curcumin phase, participants’ protein levels either stayed steady or decreased. The curcumin treatment tended to work better for participants who had higher starting levels of abnormal protein in their serum (20 g/L or more). Two participants had to drop out of the study early because of abdominal cramping and diarrhea. The research was published in the journal Clinical Cancer Research (abstract) in September.
• In the same issue of the Clinical Cancer Research journal, Dr. S. Vincent Rajkumar of the Mayo Clinic published a commentary (abstract) on the study. Rajkumar wrote that the study uses “nonstandard response criteria” to evaluate the participants’ responses to the curcumin therapy, and the results therefore will not affect how doctors treat people with MGUS. He added that curcumin needs further research.
• In a Phase 1/2 clinical trial, M. D. Anderson researchers examined curcumin’s effects on two molecular pathways known to cause tumor cells to grow and spread. Twenty-nine people with multiple myeloma were divided into two groups – one group taking curcumin alone in increasing doses and the other group taking curcumin plus Bioperine, a compound from black pepper, also in increasing doses. The researchers found that curcumin reduced the growth and spread of myeloma cells, but participants did not show any statistically significant responses. Researchers reported that their study participants did not feel any significant side effects. They presented their findings at the American Society of Hematology’s (abstract) 2007 Annual Meeting.

Due to the insufficient number of clinical trials, Medline Plus gives the use of curcumin for cancer a “C” grade, which means there is “unclear scientific evidence for this use.”

Taking curcumin

Nevertheless, some myeloma experts are enthusiastic about using curcumin to treat multiple myeloma and MGUS. Because it works against many steps in cancer, curcumin is “ideal” to use against multiple myeloma, said Bharat Aggarwal, University of Texas biochemistry professor and principal investigator for many of the M. D. Anderson curcumin studies, in an International Myeloma Foundation webcast. He widely promotes the therapeutic use of curcumin through interviews, a Web site, and a book.

Margaret Graziano, diagnosed with MGUS in 1999 and smoldering myeloma in 2005, has been taking curcumin for four years. She decided to try curcumin when her myeloma markers were worsening and her hematologist suggested she start chemotherapy.

She told her doctor she wanted to try taking curcumin for eight weeks before starting any chemotherapy. Her doctor agreed to delay treatment. After the eight weeks were up, her myeloma markers had improved to the point that her diagnosis returned to smoldering, with no need for chemotherapy. She has been considered a smoldering myelma patient ever since.

“I am almost one hundred percent positive that, had I not taken this yellow powder, I would have progressed to active myeloma by now. Just a gut feeling, though,” wrote Graziano, who takes curcumin supplements daily, in an email to The Myeloma Beacon. Her hematologist knows about the supplements she takes and supports her, she added.

Those who decide to try curcumin should keep in mind that at this time, it is regulated by the Food and Drug Administration as a dietary supplement. Companies who make it are responsible for ensuring its safety, but do not need to register with the FDA.

After a supplement is on the market, the FDA monitors its safety but not its effectiveness. There is not yet any medical standard for how much curcumin patients should take, or how often. Trials in multiple myeloma and in other cancers have tested varying doses.

Patients can read tips on how to choose supplements on the FDA’s Web site. They can also find information on potential side effects and drug interactions on Medline.

Multiple myeloma patients may have to wait a while before the efficacy of curcumin is studied according to modern medicine’s standards. Meanwhile, patients have numerous preclinical and early clinical trials and other resources to consider before choosing whether to take curcumin supplements. Patients should always consult their physicians before taking any supplements.

This article is the second part of a two-part series based on the Beacon’s conversations with Dr. Kyle. It will cover the role of clinical trials and key issues in the treatment of multiple myeloma as well as promising treatments for the future. For more information on Dr. Kyle and his approach to multiple myeloma treatment, please see part one of this series.

Clinical trials

Dr. Kyle advised that patients with multiple myeloma should go on clinical trials throughout their treatment, starting from when they are first treated. He stressed that participation in clinical trials is important because it can help answer questions about the efficacies of treatment regimens. “One of the major problems in this country is that only a small number of patients with multiple myeloma go on prospective studies,” he said. “In the United States, fewer than five percent of patients with a diagnosis of multiple myeloma go on a prospective clinical trial.”

The type of clinical trial people should choose depends on their condition. “If the patient had developing kidney failure and was in a lot of pain, you would want to treat the patient with a rapidly acting regimen,” he said. “And if the patient were not that symptomatic, then you could go to a less active regimen. That’s a judgment that the physician must make.”

Need For Stem Cell Transplants

According to Dr. Kyle, one of the key controversies among multiple myeloma doctors and researchers is “whether [stem cell] transplant is actually necessary or not in view of the novel agents thalidomide (Thalomid), Velcade (bortezomib), and Revlimid (lenalidomide).” He added, “Some physicians feel that the new agents, used either in combination or sequentially, will keep the patient in a chronic state and not require a transplant.”

However, “the three novel agents are not curative,” he said, and eventually, most people with myeloma will become resistant to the new drugs. “You need additional treatments, and one of the things that is helpful in myeloma is the transplant.”

Maintenance Therapy

“Another key controversy is whether a patient should be treated with maintenance therapy following the transplant,” said Dr. Kyle. “Our practice is not to treat the patient following the transplant. When the patient has relapsed, then we would treat the patient, or if the relapse has occurred several years after the transplant, we would seriously consider a second transplant.” He cited the need for studies comparing a maintenance regimen with no therapy.

Complementary Medicine

For those who are considering complementary therapies or alternative medicines, which are often billed as a less intense, safer choice, Dr. Kyle had some general words of caution. “In my opinion, patients should not take alternative medicines unless there is benefit or a trial in which you’re looking at benefit,” he said. He suggested that complementary therapies should be tested in clinical trials like conventional medicines.

Dr. Kyle warned against untested supplements. “Oftentimes, the person selling the supplement is the one who’s most likely to benefit. Some of these things could even be harmful.”

Emerging Therapies

Looking to the future, Dr. Kyle said that researchers are looking at potential new drugs as well as new combinations of drugs already in use. One of the new drugs he mentioned was pomalidomide (Actimid, CC-4047). “We are looking at [pomalidomide] in early studies, and in my mind, it looks very promising,” he said. There is no guarantee it will work for everyone with multiple myeloma. “It’s like all chemotherapy. Some patients will respond to Drug A and not to Drug B, and also patients will have different degrees of quality of response,” he said. “But we think that it is an active drug and will be a useful addition to the armamentarium for the treatment of myeloma.”

Dr. Kyle and his colleagues presented research on pomalidomide at this year’s Annual Meeting of the American Society of Hematology (see related Beacon news).

Other new drugs Dr. Kyle mentioned include tanespimycin, Zolinza (vorinostat), and carfilzomib. For these, as for all drugs, he is waiting to see clinical trial results. “It’s like anything else. You don’t really know what they will have to offer until you see the results of the studies,” he said. “There are many drugs over the years that have looked and sounded very, very good and have not made the grade.”

He said science’s next step is to tailor therapies to individual people based on their genetics or other features of their disease. People with different genes may respond differently to certain drugs or combinations of drugs. Scientists hope that by finding these gene-drug response relationships, they can better treat patients.

Dr. Kyle said he is also optimistic about finding a cure for multiple myeloma, “but the big question is, ‘When?’” He said the key to finding the cure is finding the cause of multiple myeloma. “That would be a very significant step forward.”

For more about Dr. Kyle’s approach to multiple myeloma treatment, please see part one of this series.

Allogeneic transplants “may very well” increase in popularity after the Blood study’s data are confirmed by clinical trials, wrote Dr. Marco Mielcarek, the study’s lead scientist, in an e-mail to the Myeloma Beacon.

People with multiple myeloma are most often treated with autologous stem cell transplants, in which patients’ own stem cells are transplanted back into their bodies, rather than allogeneic stem cell transplants, in which a healthy donor’s stem cells are transplanted to the patient. Nevertheless, experts look to allogeneic transplants as a possible cure for multiple myeloma because the healthy donor cells can attack myeloma cells.

However, allogeneic stem cell transplants carry an increased risk compared to autologous stem cell transplants. 15 percent to 40 percent of allogeneic transplant recipients die from the treatment, compared to less than 3 percent of certain autologous transplant recipients, according to the National Cancer Institute.

One major cause of death is GVHD, which happens when the donated cells attack healthy cells in the recipient’s body. Scientists differentiate between acute GVHD, which normally occurs within the first 100 days after the transplant, and chronic GVHD, which is observed after 100 days of the transplant.

In their study, scientists analyzed the medical records of people with blood cancers who were treated with allogeneic cell transplants at the Fred Hutchinson Cancer Research Center in Seattle between 2001 and 2007. Fifty-seven of these people had marrow cell donors who were taking a statin, and 12 were taking a statin and had a donor who was taking a statin. Scientists compared these groups’ reactions to their allogeneic transplants with the reactions of 464 people who did not take a statin and whose donors did not take a statin. 

Patients whose donors took a statin, and who received the immune system treatment cyclosporine after their transplant, were less likely to have severe acute GVHD in the stomach and intestines. However, patients who received the post-transplant immune system treatment tacrolimus did not see any protective effects against acute GVHD from their donors’ statin use.

When both the patients and their donors took statins, the patients were also less likely to have severe acute GVHD, but because the number of these patients was small, the results didn’t reach statistical significance.

The scientists also examined the medical records of 16 blood cancer patients who were taking a statin and had a donor who was not taking a statin. They found that these patients did not have a reduced risk of developing acute GVHD.

The scientists also found that patient or donor statin use did not decrease the risk of chronic GVHD or significantly lower cancer reoccurrence or mortality rates.

In their paper, Dr. Mielcarek’s research team presented some possible explanations for how statins may reduce GVHD. Statins, which are commonly prescribed to people with high cholesterol, heart disease or diabetes, lower cholesterol levels by blocking a cholesterol precursor. This precursor is also important to certain immune responses. Additionally, statins have immune system effects that are independent of its cholesterol-lowering effects. Combined, these effects may reduce the immune response that is the main cause of GVHD. “Statins seem to dampen ‘excessive’ immune responses through a variety of mechanisms,” wrote Dr. Mielcarek to the Beacon. “Which of these mechanisms is most relevant remains to be seen.”

Statin use seems to be relatively safe for donors, and donors who do not need statins for other conditions may be able to take them just for the donation. However, many questions remain. “Statins are among the most widely prescribed drugs worldwide; thus, they have a well established safety profile even though rare but serious adverse effects are known,” wrote Dr. Mielcarek. However, he added, scientists don’t yet know how much statin donors should take, or for how long. His research also did not address what kinds of statins are the most effective, as the study included donors who were taking different statins, including Lipitor (atorvastatin), simvastatin (Zocor) and Crestor (rosuvastatin).

“Our data provide strong evidence that donor or donor/recipient statin use confers protection against severe acute GVHD without compromising” the curative effects of an allogeneic transplant, the study’s paper concluded. The Fred Hutchinson scientists wrote that their results “might motivate” the creation of clinical trials, but suggest some questions for further research to answer first.

For more information, please see the study in Blood (abstract).

His work in myeloma began with his residency at the Mayo Clinic in the late 1950s, where he measured monoclonal protein levels in more than 6,500 myeloma and non-myeloma patients to identify a spike characteristic of multiple myeloma. He has authored more than 850 research papers and won lifetime achievement awards from the International Myeloma Foundation and the American Society of Hematology. In a 2003 editorial in Mayo Clinical Proceedings (PDF), Dr. Kenneth Anderson of Boston’s Dana-Farber Cancer Institute called Dr. Kyle “the world’s foremost expert” on multiple myeloma.

In an interview with The Myeloma Beacon, Dr. Kyle spoke about his approach to treating multiple myeloma patients; participation in clinical trials; many of the key issues for myeloma patients and physicians, including conventional and alternative treatment options; and the future of personalized medicine. This article, part one of a series of two, will cover Dr. Kyle’s approach to treatment. Part two covers the key issues and promising multiple myeloma therapies that Dr. Kyle suggested need further study.

Monoclonal Gammopathy Of Undetermined Significance And Smoldering Multiple Myeloma

During his interview with The Myeloma Beacon, Dr. Kyle first discussed the conditions that often lead to active multiple myeloma: monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma. Dr. Kyle was the first to describe MGUS and smoldering myeloma more than 30 years ago and has published many articles about both conditions since then.

Patients who have small amounts of monoclonal protein in the blood or urine are diagnosed with MGUS, he explained. If the amount of protein is larger, but the patient is asymptomatic, then the patient is designated as having smoldering multiple myeloma. Patients with symptoms are diagnosed with symptomatic multiple myeloma.

Dr. Kyle advised, “If the patient has smoldering, asymptomatic multiple myeloma, then it’s in the patient’s best interest not to treat because at the end of five years of observation, half of those patients will still be smoldering.” He added, “There are adverse side effects to any drug that you take. There’s also the cost to consider. So you’re much better off if you don’t have to take anything.”

There are some exceptions, however.  Patients with so-called “high-risk” smoldering multiple myeloma are likely to progress to symptomatic multiple myeloma within 6 to 12 months.

“Treating those patients before they develop problems with the disease is something to seriously consider,” said Dr. Kyle. He also said that a clinical trial is needed to compare survival in smoldering myeloma patients at high risk for progression between those who do and do not receive treatment.

Active Multiple Myeloma

Myeloma patients with symptoms such as anemia, pain from destruction of the bone, or an elevated calcium or creatinine level in their blood need to be treated.

“When treatment is needed, the first thing you need to decide upon is whether the patient is a candidate for an autologous stem cell transplant,” Dr. Kyle said. “If the patient is a candidate for the transplant, then one treats the patient with drugs that will reduce or kill the plasma cells in the bone marrow and not damage the stem cells.” He said most physicians will use dexamethasone (Decadron) along with thalidomide (Thalomid), Velcade (bortezomib), or Revlimid (lenalidomide). After three to four months of treatment, stem cells are collected. After collection, the patient can either continue with their original drugs or have the transplant.

Those who are not candidates for autologous stem cell transplants can be treated with melphalan (Alkeran), prednisone, and thalidomide or melphalan, prednisone, and Velcade, according to a review article by Dr. Kyle and his colleague published in August in the journal Clinical Lymphoma and Myeloma (abstract).

Another important consideration during treatment is a person’s individual genetic makeup. Dr. Kyle explained that patients with certain chromosomal abnormalities indicating poorer prognoses are “generally best treated with a Velcade-containing regimen.”

Myeloma doctors and researchers know from experience that Velcade appears to overcome the negative effects of chromosomal abnormalities. However, professional opinion is “mixed” about whether Revlimid might do the same: “We just haven’t had enough experience yet to know,” said Dr. Kyle.

Relapsed Multiple Myeloma

Dr. Kyle also discussed how he treats patients with relapsed multiple myeloma, a vital topic because almost all people who are treated for myeloma eventually relapse. When choosing a treatment regimen for a relapsed patient, “a very important consideration would be the treatment that the patient had before and how long that treatment lasted,” he said. “When a patient is treated with a drug or a combination of drugs, you need to give several courses of the drug to know whether the patient is going to respond. Generally, three or four months of therapy are necessary.”

“If that patient responds to the regimen, one generally treats the patient to the point of maximum response, provided they can tolerate the medication,” he said. “The treatment would then be stopped, and the patient would be observed without treatment.”

“If that patient remains in a response state for more than six months or, particularly, for more than a year after therapy has been discontinued, and the disease comes back at that time, then one would give that initial therapy again because the likelihood of that patient responding would be better than average with a different drug,” he said. “Also, the patient has already received that drug and knows they can tolerate it.”

However, people usually have a shorter and less effective response to a second round of therapy. Dr. Kyle explained that if a patient has a relapse within three or four months of his last treatment, “then the patient needs to go on to a new drug or a new combination of drugs.”

For more information please see part two of this series, in which Dr. Kyle discusses other myeloma treatments that still require further study.

“For the first time, we are seeing a study which is addressing the question of the early treatment of patients with smoldering myeloma,” said Dr. Brian Durie, a physician with the Cedars-Sinai Medical Center in Los Angeles and a founder of the International Myeloma Foundation, in an IMF webcast.

People with smoldering multiple myeloma have elevated blood protein and plasma cell levels, but don’t have any symptoms, such as bone pain or kidney failure. For them, the standard advice so far has been to “go home and keep in touch”—doctors check on their smoldering myeloma patients frequently, but don’t treat them until they have multiple myeloma.

The rationale is that unnecessary early treatment puts patients through chemotherapy’s grueling side effects without providing any proven benefits, and many people with smoldering myeloma never get multiple myeloma. Half of the people who have smoldering myeloma progress to cancer within the first five years, with the risk dropping to three percent per year for the next five years, then one percent per year onwards, according to a study published in The New England Journal of Medicine in 2007.

However, doctors have long suspected that certain people with smoldering myeloma are at higher risk of developing multiple myeloma and may benefit from early treatment. Researchers have found some risk factors, published in the journal Blood in 2007 and 2008 and in The New England Journal of Medicine.

It is “very likely” that in the future, studies will show that people with high-risk smoldering multiple myeloma should be treated, wrote Dr. S. Vincent Rajkumar, multiple myeloma physician and professor of medicine at the Mayo Clinic, in an e-mail to the Myeloma Beacon.

In the interim findings that were presented at the ASH meeting, scientists from cancer centers in Spain and Portugal looked at 40 smoldering myeloma patients at high risk for progressing to multiple myeloma. Some patients were not treated, while others were treated with Revlimid and dexamethasone for nine months, then with Revlimid until they developed multiple myeloma. The ASH abstract did not specify exactly how many of the 40 study participants were assigned to the treated and untreated groups.

When researchers followed up on the study participants sometime between 12 and 20 months later, none of the people treated with Revlimid and dexamethasone had developed multiple myeloma. Eight of the untreated participants developed multiple myeloma, including six people who experienced bone lesions from the cancer.

“The early results are really quite remarkable,” said Dr. Durie.

The Revlimid and dexamethasone treatment led to some side effects. Seven people developed anemia, weakness, diarrhea, or blood clots deep in the body. Five had serious side effects, including gastrointestinal bleeding, delirium, glaucoma, and infections, and two of these participants needed to drop out of the study. Two other study participants opted out.

These findings are interim results of the overall clinical trial researchers are currently conducting. They are still examining 40 additional patients and eventually plan to enroll and study 120 people overall, to determine if Revlimid and dexamethasone therapy is a viable preemptive treatment for people with high-risk smoldering myeloma. Patients may volunteer for the study at one of the participating hospitals in Spain. Please see Clinical Trial NCT00480363 for more information.

For more information on the results presented at ASH, please see abstract 614 on the ASH Meeting Web site.

“Great meeting—lots of exciting new developments for multiple myeloma,” wrote Dr. Paul Richardson, lead researcher in the study, in an e-mail to the Myeloma Beacon. He added that his trial results were “well received—especially the durability seen of benefit.”

The trial looked at 84 people with relapsed or refractory multiple myeloma who had undergone a median of five full courses of previous treatment, or about 30 months of chemotherapy.

All participants had been previously treated with Velcade, and many had also been treated with dexamethasone, Revlimid (lenalidomide), thalidomide (Thalomid) or stem cell transplants. In the trial, they were treated with perifosine and Velcade. Those whose multiple  worsened also took dexamethasone.

Seventy-three participants finished at least two cycles of the new perifosine and Velcade treatment. Thirty of those patients (41 percent) responded to the treatment, with 16 (22 percent) reaching partial response or better. The median time it took for the participants’ cancer to worsen was 6.4 months. Median overall survival time for all patients was 25 months.

To determine the side effects of the new treatment, researchers looked at all 84 participants. At least 10 percent experienced nausea, mild or moderate diarrhea, vomiting, fatigue or anorexia. These are milder side effects that the researchers managed by reducing the participants’ treatment dosages or with supportive care. At least five percent of the participants experienced severe side effects including low amounts of platelets in their blood, which can lead to abnormal bleeding; low amounts of infection-fighting cells called neutrophils; anemia; salt imbalances, which cause swelling in the brain; or severe diarrhea. Although none of the participants died from the new treatment, six people dropped out of the trial because of the severity of their side effects.

The new treatment is generally safe and effective, researchers concluded. “[It is] especially good to see [positive responses] in patients in whom prior Revlimid and Velcade has failed them,” wrote Dr. Richardson.

They have received a Special Protocol Assessment from the Food and Drug Administration (FDA), according to a press release by Keryx Biopharmaceuticals, the manufacturer of perifosine. This means that the FDA and Keryx Biopharmaceuticals have reached an agreement about the design of the Phase 3 trial. They plan to start that trial by the end of the year.

For more information, please see abstract 1869 on the ASH Meeting Web site or the Keryx Biopharmaceuticals press release.

In the July issue of Current Opinion in Hematology, Dr. Donna E. Reece, a physician and researcher at the Princess Margaret Hospital in Toronto, reviewed the current approaches to treating newly diagnosed multiple myeloma patients. Dr. Reece discussed autologous and allogeneic stem cell transplants for younger patients and treatment options for older patients.

This Beacon article focuses on Dr. Reece’s findings about the best ways to use new drugs to treat older patients who are ineligible for stem cell transplants. Findings about autologous and allogeneic stem cell transplants for younger patients were discussed in previous Beacon articles.

Improving On The Standard Of Care From The ‘60s – Melphalan And Prednisone

Since the 1960s, doctors have been treating multiple myeloma patients with melphalan (Alkeran) and prednisone. Recent studies found that adding new drugs in combination with melphalan and prednisone improves results.

A Phase 3 trial published in the New England Journal of Medicine in August 2008 found that adding Velcade to melphalan and prednisone resulted in better responses and longer times before patients’ myeloma progressed — 2 years compared to 16.6 months for people treated with melphalan and prednisone alone.

The study participants treated with Velcade, melphalan and prednisone were also more likely to have longer survival times. After 16 months, 87 percent of those participants survived, compared to 78 percent of participants taking only melphalan and prednisone.

The trial followed 682 people with multiple myeloma and had such great impact on the multiple myeloma research community that the National Comprehensive Cancer Network, a group of 21 United States cancer centers, considers treatment with melphalan, prednisone, and Velcade a “category 1 recommendation,” meaning that the cancer centers unanimously agree that there is a high-level of evidence supporting the regimen.

Dr. Reece also reviewed recent studies that tested the addition of thalidomide to melphalan and prednisone. She found that all five studies reported better responses and longer times before myeloma progression for melphalan, prednisone, and thalidomide compared to melphalan and prednisone alone.

The most recent study, a Phase 3 trial presented to the American Society of Hematology last December, found 66 percent of multiple myeloma patients treated with melphalan, prednisone, and thalidomide reached partial response or better, compared to 47 percent of people treated with melphalan and prednisone. The difference in time before disease progression was 14 months versus 10 months.

However, three of the five trials Dr. Reece studied did not find significantly different survival times, so she wrote that thalidomide’s ability to improve overall survival with melphalan and prednisone treatment is uncertain.

A New Idea — Thalidomide Or Revlimid Plus Dexamethasone

Dr. Reece found the continuous use of blood vessel-inhibiting drugs thalidomide or Revlimid plus dexamethasone (Decadron) to be a new trend in treating multiple myeloma. Several recent Phase 3 trials investigated this kind of treatment specifically in older patients. Many of these trials suggested that older patients cannot tolerate higher doses of dexamethasone.

One trial, published in the Journal of Clinical Oncology in May 2008, compared a thalidomide and dexamethasone therapy with a placebo and dexamethasone. Researchers looked at 470 multiple myeloma patients with a median age of 64.

Study participants taking thalidomide and dexamethasone had better responses than participants taking the placebo and dexamethasone. People treated with thalidomide and dexamethasone also had longer times until myeloma progression, one year and 10.6 months versus 6.5 months. However, more people taking thalidomide and dexamethasone treatment experienced severe side effects. Overall survival time was not studied.

Another trial, published in Blood in April, compared thalidomide and dexamethasone treatment with the classic melphalan and prednisone treatment in patients with a median age of 72. The study participants treated with thalidomide and dexamethasone had better responses. However, there was not a significant difference between the two treatments in time until myeloma progression, and the thalidomide-dexamethasone participants lived for 41.5 months compared to 49.5 months.

Older patients’ low tolerance for higher doses of dexamethasone was underscored by a trial published in the Journal of Clinical Oncology in May 2008. Researchers found that after one year, 96 percent of their study participants taking Revlimid and low-dose dexamethasone survived, compared to 88 percent of study participants taking Revlimid and standard-dose dexamethasone. After two years, the numbers were 87 percent and 75 percent. The study investigated 445 people with a median age of 65.

Maintenance Therapy For Elderly Patients

Dr. Reece’s review included one Phase 3 trial on maintenance therapies for older patients, published in the British Journal of Hematology in November 2008. Researchers treated 147 multiple myeloma patients, median age over 70, with thalidomide, dexamethasone, and Doxil (doxorubicin liposomal).

They then selected the 103 study participants who showed any response to treatment to receive maintenance therapy with either dexamethasone and thalidomide or dexamethasone and interferon-alpha, which can improve the body’s response to infection and slow tumor growth. Sixty-three percent of the participants treated with thalidomide and dexamethasone lived to two years, compared to 32 percent of participants treated with interferon and dexamethasone.

“The superiority of any one novel regimen has not yet been demonstrated,” Dr. Reece concluded, “and decisions for management are often made on individual . . . factors present in a given patient.”

Nevertheless, the studies illustrate the increasing options for older myeloma patients. They also show that people undergoing any modern treatment often achieve good responses and usually enjoy two years before their myeloma progresses, which is a good improvement over the 60 percent response rate and 18-month response durations, as reported by the NCCN, from the days when melphalan and prednisone were the standard choice.

For more information, please see the review in Current Opinion in Hematology (abstract).

ASH annual meetings keep hematologists up to date on research and treatment advances from the past year. According to ASH, the meeting has “a superb educational program,” “cutting-edge scientific sessions,” and presentations that “contain the latest and most exciting developments in scientific research.”

More than 20,000 doctors, scientists, and others from across the nation and world are expected to attend this year’s ASH meeting.

The Myeloma Beacon will be covering some of the meeting’s most important multiple myeloma presentations in the coming weeks.

New Combinations Using Thalidomide, Revlimid, And Velcade

Many of this year’s presentations will compare different treatment regimens using some of the most effective myeloma drugs that have come out over the past decade, such as thalidomide (Thalomid), Revlimid (lenalidomide), and Velcade (bortezomib). Scientists attending the ASH meeting are continuing to develop these new drugs and combinations of drugs to further improve treatment for myeloma patients.

At the meeting, scientists will present results from clinical trials involving many different subsets of participants, including elderly patients, newly-diagnosed patients, and more.

Highlights include an update from the IFM2005-01 Phase 3 trial, with progression-free survival times for people with multiple myeloma treated with one of two induction therapies, Velcade and dexamethasone (Decadron) or vincristine, doxorubicin (Adriamycin), and dexamethasone.

Researchers working on the German DSMM XIa Phase 2/3 trial will present results from 300 patients treated with an induction therapy of Velcade, cyclophosphamide, and dexamethasone.

Investigators from an Italian Phase 3 study will present Velcade, melphalan, prednisone, and thalidomide followed by maintenance therapy of Velcade plus thalidomide as an initial treatment for elderly people with multiple myeloma.

New Treatments Under Development

Beyond therapies using currently-available drugs, several ASH Annual Meeting presenters will unveil results from Phase 1 and Phase 2 clinical trials of new drugs in the fight against multiple myeloma.

In particular, there will be many presentations on carfilzomib, pomalidomide (Actimid, CC-4047), and Zolinza (vorinostat). There will also be presentations on tanespimycin, perifosine, panobinostat, NPI-0052, CEP-18770, Torisel (temsirolimus), elotuzumab, Afinitor (everolimus), and ACE-011.

Personalized Therapy

Backing the search for new therapies are studies on multiple myeloma genes, proteins, and cells. This year’s ASH Annual Meeting will feature several sessions on molecular and genetic research. There will be new findings about the particular gene abnormalities some people with multiple myeloma have as well as how those genes might affect patient responses to different therapies. Finding out about these genes is a first step towards personalized therapy, which many experts see as the wave of the future.

Long-Term Survivors Of Multiple Myeloma

As research continues to advance, doctors can look further in the future for their patients. This year’s ASH meeting will include presentations on the few people —less than two percent of people with multiple myeloma, according to some University of Texas researchers— who have lived with multiple myeloma for more than 10 years. ASH Meeting presenters will try to characterize long-term survivors and how they were treated, in hopes of increasing that two percent figure in the future.

Social And Public Policy

ASH will also consider social and public policy issues in its meeting this year, with a physician education session on health care disparities in people with blood diseases. For multiple myeloma, specifically, researchers will give poster presentations on the out-of-pocket costs for people with multiple myeloma and on ethnic disparities in access to stem cell transplants.

For more information on ASH’s 51st Annual Meeting, including presentation abstracts, the final schedule, and information on attending, please see the American Society of Hematology Web site.

In the review, Dr. Reece discussed autologous and allogeneic stem cell transplants for younger patients and treatment options for older patients.  This Beacon article focuses on Dr. Reece’s findings about allogeneic stem cell transplants. Findings about autologous stem cell transplants were discussed in a previous Beacon article. Treatment options for older patients will be covered in part three of this series.

In allogeneic stem cell transplants, stem cells are collected from a healthy donor and then placed into the patient’s body after chemotherapy. Though not as commonly used in multiple myeloma treatment as autologous stem cell transplants, allogeneic stem cell transplants continue to interest myeloma researchers because stem cells from allogeneic transplants are able to work against the patient’s myeloma cells in a “possibly curative” reaction, according to the National Cancer Institute.

Authors of a study published in the journal Blood in April stated that “despite recent advances, allografting remains the only potential cure for myeloma.”

In her review, Dr. Reece discussed the effectiveness of allogeneic transplants, especially compared to autologous transplants. The jury is still out, Reece concluded.

The newest way that allogeneic stem cell transplants are being used is following an autologous transplant and nonmyeloablative, or less intense, chemotherapy.

Several cancer centers in the U.S. and Italy collaborated to produce a study that treated 102 people with newly-diagnosed multiple myeloma and followed up on them after six years. Fifty-nine participants achieved complete remissions and the participants’ disease remained stable for a median of three years. The biggest problem with the treatment was graft-versus-host disease, in which the donated cells attack the transplant recipient’s body, resulting in jaundice, rashes, and other symptoms, as well as special vulnerability to infections. Eighteen percent of the participants died from causes not related to relapse, almost all from graft-versus-host disease or infections. For more information on this collaborative study, please see the previous Beacon coverage or the original Blood article.

In another study on nonmyeloablative allogeneic transplants, an international team of scientists analyzed how people’s individual genetic makeup may affect their response to stem cell transplants. They found allogeneic stem cell transplants helped people with a genetic abnormality called t(4;14), in which DNA is moved between the fourth chromosome in a person’s genes to the 14th chromosome. However, study participants with a genetic abnormality called del(17p3) fared worse than other participants. For more information on this genetic study, please see the article in the journal Leukemia.

To assess allogeneic transplants’ promise against results from autologous transplants, Reece examined three studies. Two of the three studies found that people who were treated with allogeneic transplants had shorter median times of stable disease than people who underwent autologous transplants. One study found that people who underwent allogeneic transplants had shorter median overall length of survival, while the other two studies were still in the process of collecting survival data. For more information on these studies, please see the article published in 2007 in the New England Journal of Medicine, and the clinical trial and correspondence published in Blood last year.

Reece’s review gave a picture of a treatment that is improving, but not yet ready for widespread use. The 18 percent rate of death that the U.S.-Italy study found was lower than mortality rates associated with allogeneic transplants in the past.

However, comparative studies show that at this time, allogeneic stem cell transplants do not improve lifespans. “The role of allogeneic stem cell transplants remains to be defined,” Reece concluded.

For more information, please see the review in Current Opinion in Hematology (abstract).

In the review, Dr. Reece discussed autologous and allogeneic stem cell transplants for younger patients and treatment options for older patients. This Beacon article focuses on Dr. Reece’s findings about autologous stem cell transplants, and upcoming Beacon articles will focus on allogeneic stem cell transplants and treatment options for older patients.

Autologous stem cell transplantation – the process of collecting stem cells and returning them to the same individual – following chemotherapy is a common treatment option for newly diagnosed myeloma patients. Stem cell transplantation replaces the stem cells destroyed during the chemotherapy treatment, leading to higher response rates and longer survival.

In her review, Dr. Reece covered ongoing research on the steps taken before, during, and after transplant treatments. These steps include pre-transplant induction therapies, which serve as the first step in reducing cancer cells; high-dose treatments, which prepare the body for the transplant; the use of two transplants instead of one; and after-transplant maintenance therapies.

The Importance Of Improving Induction Therapies

As the Beacon previously reported, multiple myeloma researchers are becoming increasingly aware of the importance of complete response, which is a standardized measure that uses bone marrow and immunofixation tests to determine how well patients respond to treatment. Complete response is emerging as an important predictor of progression-free survival and longer overall survival.

Most studies look at the relationship between response and overall lifespan after treatment. However, it may also be important to reach complete response after induction therapy (and before the autologous stem cell transplant). Those who reach complete response after induction therapy may achieve greater overall survival after their entire course of treatment.

Thus, doctors hope to further develop multiple myeloma treatment by improving, and therefore increasing complete response to, induction therapies. Reece cited two Phase 3 clinical trials reported last year that compare different induction regimens.

One, presented to the American Society of Clinical Oncology, found that a Velcade (bortezomib) and dexamethasone (Decadron) induction regimen helped more people reach complete or very good partial response than did a commonly-used regimen of vincristine, doxorubicin (Adriamycin), and dexamethasone. Sixty-eight percent of people treated with Velcade and dexamethasone had a least a very good partial response, compared to 27 percent of people treated with vincristine, doxorubicin, and dexamethasone. The better responses persisted after the study participants received stem cell transplants.

The other trial, presented to the American Society of Hematology, found a Velcade, thalidomide (Thalomid), and dexamethasone induction regimen caused a very good partial response or better in 92 percent of the study participants. In comparison, Velcade and thalidomide without dexamethasone caused a similar response in 79 percent of participants.

New High-Dose Treatments

Researchers are also conducting clinical trials of high-dose treatments using newly-discovered drugs. A group of researchers in France found that Velcade and high-dose melphalan (Alkeran) make for a “safe and highly effective” preparatory treatment in a Phase 2 trial, which was presented to the American Society of Hematology in 2008. In another Phase 2 trial published in the same year, M. D. Anderson Cancer Center researchers found arsenic trioxide, ascorbic acid, and melphalan to be “safe and well tolerated.” Their work appeared in the journal Biology of Blood and Marrow Transplantation.

Tandem Autologous Stem Cell Transplants

Tandem autologous stem cell transplants, or two transplants performed within six months of each other, is a controversial potential treatment. Reece wrote that researchers are interested in tandem transplants because they can help people reach complete response at relatively low costs.

She highlighted two large, conflicting recent studies on the tandem autologous stem cell transplant treatment. One, published in the Journal of the National Cancer Institute in July, not only reported that the treatment reaped no benefit to overall survival, but also correlated the treatment with higher mortality rates due to complications with the transplants. Another study, published in the journal Experimental Hematology in 2008, found that second transplants improved lifespan.

After-Transplant Therapies

Several recent studies have found that thalidomide helps people achieve longer remissions, but they differ on whether the drug improves overall lifespan as well. A study published in the Journal of Clinical Oncology in March found that thalidomide combined with prednisone improved both remission durations and lifespan after stem cell transplants. However, two studies published in 2006 reported improved remission durations without improved lifespan: one from the New England Journal of Medicine and one from Blood.

Replacing Autologous Stem Cell Transplants With Chemotherapy

One of the newest and most debated issues in stem cell transplant therapy for multiple myeloma is whether drugs like Revlimid (lenalidomide), thalidomide, and Velcade can replace transplants altogether. In an interview with the Beacon, Dr. Robert Kyle, a leading multiple myeloma physician with the Mayo Clinic, identified the necessity of transplants as a major controversy in myeloma research.

Reece touched on the debate in her review, writing that there is no answer yet, “but it is to be hoped that future trials will address this important issue.”

Many studies have come out in recent years as researchers work to improve autologous stem cell transplant therapy and analyze the effects of new drugs. However, more testing is necessary before the new treatment ideas may become widely used or the standard of care for multiple myeloma.

Overall, Reece wrote that “a number of questions remain about the optimal strategy” for myeloma management.

However, the wealth of findings and advancements that appears in Reece’s review suggests that myeloma research is moving forward, exposing new directions for treatment.

For more information, please see the review in Current Opinion in Hematology (abstract).

Steroid-based drugs such as dexamethasone (Decadron) are common and effective multiple myeloma treatments but can have serious side effects, especially for people with diabetes or high blood pressure. Those with diabetes or high blood pressure can still take steroid drugs, but may need extra monitoring, according to the International Myeloma Foundation (pdf).

The State University of New York study looked at patients with relapsed multiple myeloma, plasma cell leukemia, or Waldenstrom macroglobulinemia who were receiving treatment at the Roswell Park Cancer Institute in Buffalo, New York.  Study participants were put on a four-week schedule of Velcade, Doxil and thalidomide.  Their progress was monitored after each four-week interval for four to six months.

After four to six cycles, four participants achieved complete remission and six achieved partial remission. Five out of the remaining 13 had minimal response or reached stable disease. Two people dropped out of the study early because they could not tolerate the side effects of the treatment.

The most common side effects, affecting at least half of the participants, included low numbers of platelets and infection-fighting white blood cells called neutrophils; mild paresthesia, or prickling feelings in the limbs, and moderate fatigue that made some everyday tasks difficult.

In their paper, the researchers said their steroid-free regimen was “promising” and called for research to repeat their results with a bigger pool of participants. The researchers also plan to study the regimen as a first-line treatment.

For more information, please see the study in the journal Leukemia and Lymphoma (abstract).

During an autologous stem cell transplant, physicians collect a patient’s stem cells in the early stages of the patient’s anti-myeloma drug regimen, and return these same cells to the individual after the regimen is complete. Transplantation is a common treatment usually given to any multiple myeloma patients who can tolerate it.

Currently, doctors collect stem cells from multiple myeloma patients after about four cycles of an initial drug regimen using some combination of dexamethasone (Decadron), Revlimid, thalidomide, and Velcade.

The transplantation of bone marrow cells as a myeloma treatment was first studied in 1957, according to the American Society of Hematology’s 50th anniversary review.  Usage of stem cell transplants picked up throughout the 1980s.

Meanwhile, some of the drugs most familiar to people with multiple myeloma today were approved within the last 15 years. Velcade was first synthesized in 1995; a landmark study helped establish thalidomide as a multiple myeloma drug in 1999; and Revlimid was approved by the United States Food and Drug Administration in 2006.

The long gap between when stem cell transplants came into use and when the latest multiple myeloma drugs hit the market means that people with multiple myeloma are treated significantly different now compared to when autologous stem cell transplants were first used. The advances in myeloma treatment have created debate about how stem cell transplants and the new drugs should be used together.

Some researchers argue that the new drugs are so effective that people do not need to have stem cell transplants at all. The IMWG article, on the other hand, says that there is not enough long-term data about survival of people who are treated with these drugs without transplants to make that judgment.

Others worry that the new drugs make stem cells difficult to collect for autologous transplants. To respond to these concerns, 25 IMWG physicians and scientists reviewed published studies on the drugs’ effects on stem cell transplants. They found that:

• Revlimid can interfere with collecting enough stem cells for a transplant. Two studies, published in the journals Leukemia and Biology of Blood and Marrow Transplantation, found that use of Revlimid was the most important factor in doctors’ ability to collect enough stem cells.
• Thalidomide has little to no negative effects on stem cell transplants.
• The results from studies on Velcade’s effects on stem cell collection are mixed.

Since Revlimid can decrease the number of stem cells collected, the IMWG recommends doctors co-administer granulocyte colony-stimulating factor, a medicine that increases the number of white blood cells the body makes.

Scientists do not know exactly how Revlimid decreases the number of stem cells collected from patients. Therefore, the IMWG researchers wrote that “every effort should be made to enroll these patients in clinical trials evaluating these questions.”

In their Blood article, the IMWG authors disclosed that 22 of them had some financial ties to pharmaceutical companies, including Millennium, manufacturer of Velcade, and Celgene, manufacturer of Revlimid and Thalomid. The most common ties were through clinical trial funding or participation in advisory boards.

For more information on the new IMWG recommendations, please see the article in the journal Blood.

Resveratrol is a type of polyphenol, which is a plant compound that has anti-oxidant properties. Grape skins have high concentrations of resveratrol, which is why it appears abundantly in red wine. Peanuts, raspberries, the herb knotweed, and certain other plants also have high concentrations of the compound. Resveratrol‘s anti-cancer properties were first found in 1997, and the compound has been intensely studied since.

The Latest Research

The most recent research in cell cultures, or myeloma cells bred and maintained in labs, finds that resveratrol can kill myeloma cells and reduce the symptoms of multiple myeloma in several ways:

• University of Texas scientists showed that resveratrol suppressed the genes that protect myeloma cells from dying. In experiments, resveratrol killed myeloma cells that were resistant to chemotherapy and enhanced the effects of Velcade (bortezomib) and thalidomide (Thalomid). The scientists published their study in the journal Blood (abstract) in December 2006.
• Scientists at Huazhong University of Science and Technology in Wuhan, China, showed that resveratrol suppresses proteins that myeloma cells need to grow quickly. However, they found that the doses they used were much higher than the levels found in people after drinking red wine or even eating pure resveratrol. They suggested further studies look at applying resveratrol directly to tumors. The journal Acta Pharmacologica Sinica (abstract) published their results in November 2006.
• A study done at the Vejle Hospital in Denmark supported findings that resveratrol enhances myeloma cell death. Additionally, the Vejle scientists showed that resveratrol healed bones. It inhibited the cells that break down bone and worked with vitamin D to build new bone. The study appeared in the journal Cancer Research in November 2005.

All the studies suggested that resveratrol is relatively safe. It often causes fewer side effects than the chemotherapy drugs commonly used today. Resveratrol is an “ideal molecule” for chemotherapy, wrote scientists in a review published in the Archives of Biochemistry and Biophysics (abstract) in January.

“I am hoping safe agents like resveratrol are pursued actively,” wrote Dr. Bharat Aggarwal, a University of Texas cancer researcher, in an e-mail to the Myeloma Beacon. “Cell culture data tells us that resveratrol has the potential against multiple myeloma cells but it is not conclusive.”

There are a “million reasons” why cell line studies might not translate directly to treatments, he continued. “Perhaps the most important is that the human body is more complex than a few cells in culture.”

In his Blood publication, he and his colleagues wrote that resveratrol’s apparent safety and efficacy merited clinical trials.

The Myeloma Beacon found one clinical trial on resveratrol and multiple myeloma. The Phase 2, GlaxoSmithKline trial is currently recruiting participants in Denmark and the United Kingdom. However, no other ongoing trials or published results could be found.

“We need more trials,” wrote Aggarwal.

Drinking Red Wine

How the published research applies to red wine consumption is uncertain. There are no studies on drinking red wine and multiple myeloma. Studies about red wine and other cancers had mixed results.

In February, the Journal of the National Cancer Institute (abstract) published research that showed that drinking any alcohol, including red wine, increased women’s risk of some cancers but decreased women’s risk of other cancers.

Red wine’s effects on prostate cancer made the news in 2007, but the newest research suggests otherwise. A 2005 Fred Hutchinson Cancer Research Center study found that drinking red wine was associated with lowered risk, but studies since have seen no correlation. Examples include a June Kaiser Permanente (abstract) study and a 2007 Johns Hopkins study, both published in the International Journal of Cancer.

Resveratrol Supplements

Considering the positive results of resveratrol cell line studies, however, people with multiple myeloma may decide to try one of the many resveratrol capsules and powders on the market. Those who do should keep in mind that at the moment, resveratrol is regulated by the Food and Drug Administration as a dietary supplement. Companies who make it are responsible for ensuring it is safe, but do not need to register with the FDA.

After a supplement is on the market, the FDA monitors its safety but not its effectiveness. There is not yet any medical standard for how much resveratrol patients should take, or how often. Patients can read tips on how to choose supplements on the FDA’s Web site.

Though many companies follow the rules, patients should beware of those who do not. One resveratrol manufacturer drew high-profile lawsuits and criticism last month, reported the New York Times. Business watchdog the Better Business Bureau slammed FWM Laboratories Inc.’s “grossly misleading” advertising and fraudulent business practices.

It may be a while yet before resveratrol is tested to modern medicine’s standards of safety and efficacy. Meanwhile, patients have many factors to consider before choosing to drink red wine in moderation or to take resveratrol supplements. Patients should always consult their physician before taking resveratrol or changing their consumption of red wine.

Perhaps one reason why Velcade is especially effective in treating multiple myeloma is because myeloma cells do not secrete GRP-78. Nevertheless, some people with multiple myeloma are resistant to Velcade treatment. This research, besides finding important knowledge about a variety of cancers that do form solid tumors, may help scientists eliminate one possible cause of Velcade resistance in multiple myeloma.

Researchers at the Innsbruck Medical University in Austria hypothesized that some solid tumor cells secrete something that protects them from dying from Velcade’s effects. They performed a series of experiments to find this protective molecule and found GRP-78. They then tested GRP-78 to see how it interfered with Velcade.

To begin their experiments, they transferred different kinds of tumor cells into developing chicks and some human cells harvested from umbilical cords. They treated the chick embryos and human cells with Velcade.

To determine if the treatment was working, they looked at blood vessel growth in the tumors. Several recent studies showed that one of the ways Velcade works against cancer is by preventing blood vessels from growing in tumors, starving the tumor cells of blood.

Some cancers responded to the treatment and some did not:

• Velcade treatment did not work for colorectal carcinoma, melanoma, or prostate carcinoma, because Velcade’s action on blood vessels was blocked
• Velcade treatment worked for multiple myeloma, breast cancer, and glioblastoma, because Velcade’s action prevented blood vessel growth

To find out what might make certain cancer cells resistant to Velcade, the researchers blended and separated the Velcade-resistant colorectal carcinoma cells into their component parts: proteins, fluids, and more. They tested each of these components by adding them to some human embryonic cells, along with Velcade, to see which of these components blocked Velcade’s action on blood vessels.

They found that the only component that blocked Velcade’s action was the protein GRP-78.

By blending and separating other cells, they determined that though many cells contain GRP-78, including non-resistant cancer cells and normal human embryonic cells, resistant cancer cells have extra high levels of the protein.

To confirm GRP-78’s resistant activity, researchers added it to the non-resistant multiple myeloma cells. They then tried to treat those cells with Velcade. The treatment did not work, suggesting that GRP-78 conferred Velcade resistance to the previously non-resistant myeloma cells.

Next, they removed GRP-78 from resistant cancer cells and treated those cells with Velcade. The treatment worked. The researchers concluded that without GRP-78, previously Velcade-resistant cells lost their resistance, so GRP-78 must be responsible for Velcade resistance.

Lastly, the researchers performed some experiments to find out how GRP-78 interferes with Velcade. When cells treated with Velcade sense that they contain abnormal proteins and are deprived of blood, they begin to die. However, the researchers found that GRP-78 prevents cellular death. The researchers identified the pathway GRP-78 uses to prevent cellular death and suggested further studies on administering certain other proteins alongside Velcade in cancer treatments, to help counter resistance.

Meanwhile, the molecular basis of Velcade resistance in multiple myeloma remains “elusive,” according to a 2008 study (abstract) published in the journal Blood. Recent studies have discovered some genes and proteins involved, however. These include studies published in the Journal of Clinical Oncology (abstract) in 2009, in Oncogene (abstract) in 2005, and the 2008 Blood paper. In 2008, Blood also published a review of science’s current understanding of Velcade resistance.

Scientists hope that by discovering what causes Velcade resistance, perhaps in experiments similar to the Innsbruck Medical University’s GRP-78 study, they can develop treatments to overcome it.

Please see the article in the journal Blood for more information on the GRP-78 study (abstract).

After a boyhood fixing motorcycles and rider lawnmowers, Woodward is now a New York-based mechanical engineer who researches the fluid dynamics of blood. He has lived with multiple myeloma since his diagnosis just after Christmas in 2005.

Woodward told the Myeloma Beacon that at the time he was diagnosed, he had never heard of multiple myeloma. But as a researcher familiar with reading biomedical literature, he said, “it was pretty easy for me to figure out what the disease was and get lots of technical information.” He keeps up with current information on the disease by subscribing to alerts from the journals Cancer and Hematology, the International Myeloma Foundation, the Multiple Myeloma Research Foundation, and the Myeloma Minute.

He soon found that the most disorienting aspect of his diagnosis was dealing with the overwhelming amount of available information.

But for him, more important than all this technical information was finding and connecting with people who had multiple myeloma and other cancers. He wanted to reach others who understood the trauma of getting diagnosed with an incurable disease.

He found support through Gilda’s Club and through his blog, “Laughing Plasma Cells.”

He described his cancer support group as filled with hope, acceptance, laughter, and enthusiasm. He called it his second home. Extending a welcoming hand to new members gave him meaning and purpose.

As for his blog, Woodward created it to keep his friends and family updated. He found it emotionally exhausting to answer questions and calls from his many concerned friends after the initial diagnosis, so he started blogging to keep in touch. Though he said that he continues to write mainly for his family and friends, writing his own blog and reading others’ blogs have helped Woodward garner a worldwide network of friends, calling other bloggers “phenomenal resources.”

He has advice for those newly diagnosed with multiple myeloma: “I tell them that the most important thing to do is to find other people with multiple myeloma that you can be with personally. If you’re not finding multiple myeloma people, probably the next best thing is a cancer group. Those types of things help with that emotional side of cancer, which can be an intense side of cancer, especially when you have a cancer that they never talk about curing and the life expectancy is relatively short. That can be daunting and life changing.”

In his Gilda’s Club speech, he shared some insight into what it was like for a builder, fixer, and explorer like him to get diagnosed with multiple myeloma. “My ship ran aground. I can’t fix what’s eating at my bones from the inside out,” he said. “The fear paralyzed my confidence and shattered the lives of those that love me dearly.”

However, after seeking and finding support, Woodward had a positive assessment of his life after diagnosis. “I wouldn’t wish a diagnosis like this on anyone,” he said, “but I think that my life is better now than before. I am happier now than before and I’m more fulfilled and I have many more friends than I had before and I guess I’m a little more open and I reach out to more people.”

Early this year, he and his wife adopted a starving stray cat they found underneath their porch. They named the cat Hope.

“I look for hope in being able to touch friends and people around me in a positive, lasting, and enduring way,” Woodward said. “I find hope in living through example.”

For more information on Scott Woodward, please see his blog, “Laughing Plasma Cells.”

Whether the study’s findings will apply to patients not in clinical trials is up for debate. However, the findings are very important to doctors doing clinical trials with patients, wrote Dr. S. Vincent Rajkumar, lead researcher of the study, in an e-mail to the Myeloma Beacon. Clinical trials depend on all researchers reporting complete response in the same way, so that scientists can compare treatments studied under different trials. Rajkumar’s research confirms the need for bone marrow exams to report complete response.

Bone marrow exams look for the amount of plasma cells in the bone marrow. In their published paper, the Mayo Clinic scientists wrote that the exams can be cumbersome and uncomfortable for patients, so some doctors skip them.

The current standard is for doctors to perform three lab tests to see how well their patients are faring after experimental treatment: a bone marrow exam, serum immunofixation, and urine immunofixation. Some doctors argue that just doing serum and urine immunofixation is enough because if those results show that a patient has completely responded to his or her treatment, then it is unlikely that bone marrow exam results will show otherwise.

Before the study, “many, including me, felt that the bone marrow requirement may not be needed, and it basically put patients through an unnecessary procedure,” wrote Rajkumar.

However, his research found that this notion was incorrect, and that doctors should continue performing all three tests.

Rajkumar and his colleagues examined data from 92 people with treated multiple myeloma. The data came from 1995 and afterwards. The study participants all had good results from serum and urine immunofixation and had a bone marrow exam within 30 days of their immunofixation tests. In 14 percent of these people, bone marrow exams showed that they still had five percent or more plasma cells. This result meant that they did not completely respond to treatment, even though their serum and urine immunofixation results showed improvement.

Rajkumar emphasized that the study was geared towards doctors in research settings. The study was not designed to test whether patients who are not in clinical trials need bone marrow exams. “That is a separate, controversial issue,” Rajkumar wrote.

Nevertheless, the study’s results showed it may be important for doctors to know their patients’ plasma cell amounts because these amounts are correlated with survival times. After they achieved good serum and urine immunofixation results, the study participants who had less than five percent plasma cells on average lived significantly longer than those who had five percent or more plasma cells. However, there was no significant difference in how long the people in these two groups lived after their initial diagnosis.

Researchers also found that adding another exam that looked at free light chains did not make the results more accurate. Ten percent of their study participants with normal results from a free light chain exam still had five percent or more plasma cells in their bone marrow.

The study paper recommended that others research what happens when doctors keep treating patients who have good serum and urine immunofixation results, but have five percent or more plasma cells. This can help these patients fully recover their blood function and improve survival rates.

For more information, please see the article in the journal Blood.

According to CyDex’s press release, the advantages of the new treatment are its one-vial packaging, gentler formula, and increased stability at room temperature. “These advantages have the potential to enable doctors to safely achieve a higher dose intensity of pre-transplant chemotherapy, which could lead to better therapeutic outcomes,” said Dr. Parameswaran Hari, clinical director of the Adult Bone Marrow Transplant Program and an associate professor at the Medical College of Wisconsin.

CyDex’s first Phase 2 trial will start this August with 24 study subjects, but is not yet open to recruiting participants according to the National Institutes of Health’s ClinicalTrials.gov. CyDex estimated that it will finish its tests in December 2010.

In December 2008, the FDA gave orphan drug designation to CyDex’s Proylene Glycol-Free Melphalan HCL as a preparatory treatment for stem cell transplants. This “orphan status,” as the FDA calls it, gives companies tax credits and marketing incentives to make products for diseases that affect less than 200,000 people in the United States. CyDex will have exclusive marketing rights to its new melphalan for seven years.

For more information, please see the CyDex Pharmaceuticals press release (pdf) and the ClinicalTrials.gov document on CyDex’s upcoming Phase 2 trial.

Scientists at the Mayo Clinic looked at blood serum samples from 911 blood-related, first-degree relatives of people with either multiple myeloma or MGUS. All the study participants were 40 or over.

The researchers then compared the study participants’ rates of MGUS with rates of MGUS found in a previous general health study on 28,000 residents of Olmstead County, Minnesota, who were 50 or older. The researchers used the Olmstead County data to calculate what rates of MGUS they expected to find in the general population.

In both the new Mayo Clinic study and in the older Olmstead County study, clinicians diagnosed MGUS using a lab test called serum protein electrophoresis. Serum protein electrophoresis is less sensitive than some other tests available for MGUS, such as serum immunofixation and the free light chain assay.

Calculations of absolute risk, on which relative risk figures are based, took age and sex into account.

Doctors could use their findings and the results of any follow-up studies to help determine who is at risk for MGUS, and how to treat people with MGUS, based on whether or not they have a family history of the condition, the researchers wrote in their paper.

They also wrote that the increased risk they found “implies shared genes and/or environment.” They argue in their paper that genetic factors are at play, based on previously done case studies on specific families, and on previous research that found racial differences in MGUS rates, including similar rates of MGUS among people of African descent living in the United States and in Ghana. However, the exact way in which genes contribute to MGUS is not known.

For more information on the increased risk of developing myeloma after an MGUS diagnosis, please see the related Beacon article. For more information about this Mayo Clinic study, please see the article in the journal Blood.

Wherever a patient goes for treatment, the health care providers there will make sure his fluid intake is right for his condition. Often, patients will have to stay in a hospital overnight to be monitored and to receive other treatments, which might include certain drugs and intravenous fluids. (For more details on kidney failure treatments, please see the related Beacon article.)

Because acute kidney failure can progress quickly in people with multiple myeloma, the need for this hospital visit may come up suddenly, disrupting patients’ schedules and causing stress. Drug therapies may continue after the initial hospital visit.

Depending on patients’ eligibility, doctors may prescribe a plasmapheresis, or plasma exchange, regimen. The procedure takes one to three hours. After that, most people can return to most of their normal activities.

In a paper published in the journal Leukemia, doctors from the University of Athens School of Medicine report that for their patients, they repeat a plasma exchange procedure every two or three days to a maximum of four or five sessions. This means that people undergoing plasma exchange for myeloma-related kidney failure will spend a small part of their day getting treatment every few days for less than two weeks. Plasmapheresis usually is not a long-term treatment.

For more severe kidney failure, in which most of the kidney’s ability is lost, patients need to have hemodialysis or peritoneal dialysis. Hemodialysis filters the blood through a machine. It is the most common form of dialysis, and often what people mean when they talk about dialysis. Peritoneal dialysis uses the filtering ability of the peritoneum, or the lining of the abdomen, to clean the blood. A special fluid called the dialysate is introduced into the abdomen. The dialysate draws wastes from the blood into the peritoneum. Then the fluid is drained out of the body and thrown away.

People undergoing hemodialysis will usually visit either a standalone dialysis center or a hospital three to four times a week for three to five hours at a time.

Patients can also have hemodialysis at home on varying schedules, including shorter but more frequent treatments and nighttime treatments. People who use home hemodialysis report that they have more energy, sleep better, and enjoy better quality of life.

However, those who choose this option will have to take on the responsibility for monitoring their own progress, making sure they are getting enough treatments, and maintaining their dialysis machine. Usually, they will need someone to help them, such as a family member or a friend. The helper and the patient have to be trained for four to eight weeks, according to DaVita, a company that provides dialysis facilities to more than 2,000 clinics and hospitals in the United States.

Peritoneal dialysis requires daily treatments on varying schedules, amounting to several hours a day, depending on the type of peritoneal dialysis patients and their doctors choose. Three major types are continuous ambulatory peritoneal dialysis, continuous cycling peritoneal dialysis, and intermittent peritoneal dialysis. For all peritoneal dialysis types, a doctor will put a small, soft, flexible tube called a catheter in the patient’s abdomen. The dialysate goes into the abdomen through the catheter. The catheter will stay there permanently, and the patient will have to keep it clean and dry.

Peritoneal dialysis is often done at home, at work, or while traveling. For continuous cycling peritoneal dialysis and intermittent peritoneal dialysis, most or all of the hours required are fulfilled at night, while the patient is sleeping. Training for patients and any helpers takes two weeks, according to DaVita.

People undergoing any kind of kidney dialysis will need to make changes to their diets as directed by their doctors and may need some additional medications. Otherwise, if there are no complications, patients can go on with most of their daily activities when they are not getting treated. Though travel may be difficult for patients undergoing dialysis, a recent article in a Madison, Wisconsin newspaper included the story of Sabine Lobitz, who has multiple myeloma and travels with her home hemodialysis equipment. To read more about Ms. Lobitz, please see the Capital Times article.

Managing multiple myeloma-caused kidney failure takes up a significant amount of patients’ time and attention, but there are many options for treatment, so patients can choose what will work best for them.

For more information on kidney failure in multiple myeloma, please see the other Beacon articles in this series and related Beacon news articles.

Time Needed for Major Kidney Failure Treatments for Multiple Myeloma Patients

*Unlike the other treatments in this table, people using continuous ambulatory peritoneal dialysis can stay mobile during this time. They only need to tend to their dialysis during the 30-minute draining time

More specifically, the study found that there was a difference of 75 percent relative risk between vegetarians and meat eaters for developing multiple myeloma.

For this research, scientists at the University of Oxford compared vegetarians’ and meat eaters’ risks of developing cancer. This was done by analyzing data about more than 61,000 British men and women over the course of 12 years.

By the time of follow-up, 3,350 of the research participants were diagnosed with cancer. The scientists broke down their findings into risk differences between vegetarians and meat eaters for 20 different kinds of cancer.

For blood, stomach, and bladder cancers, they found significantly lower risk among vegetarians compared to meat eaters. They called their blood cancer data their “most striking finding,” with both the greatest percent difference in risk and a large pool of people to base their conclusions on—257 of the study participants had blood cancers.

Both Professor Tim Key, first author of the study and member of the Cancer Epidemiology Unit at the University of Oxford, and Sara Hiom, Cancer Research U.K. director of health information, stress the need for more research to replicate the study’s results and to discover why meat consumption might affect the development of cancer, particularly blood cancers.

Meanwhile, Hiom advises that people “eat a healthy, balanced diet high in fiber, fruit, and vegetables and low in saturated fat, salt, and red and processed meat.”

Key and his colleagues’ data came from two previous studies in the U.K., the Oxford Vegetarian Study and the EPIC-Oxford cohort. The results were found to be independent of many other possible cancer-causing factors including age, smoking, alcohol use, obesity, and exercise habits.

For more information, please see the press release from Cancer Research UK . The full text of the research paper is also available for free from the British Journal of Cancer.

Although scientists and doctors do not know the exact causes of multiple myeloma, doctors do know some risk factors that make people more likely to develop multiple myeloma. However, many people who have more than one of these identified risk factors do not get the disease, and many people who get the disease do not display all these risk factors.

Instead, according to the University of Virginia Health System, it is advised for people to know the risk factors for any disease to help them guide their choices about getting monitored and tested.

• Age: Risk for multiple myeloma increases with age. Less than one percent of newly-diagnosed people are younger than 35, and the average age of newly-diagnosed people is about 65.
• Gender: Men are at higher risk than women. The American Cancer Society estimated that in 2009, 11,680 men and 8,900 women will be diagnosed with multiple myeloma.
• Race: Multiple myeloma occurs almost twice as often in African-Americans than in Caucasian-Americans. The reason for this difference is not known.
• Other Plasma Cell Conditions: People who have one myeloma lesion, called a solitary plasmacytoma, or who have monoclonal gammopathy of undetermined significance (MGUS), have higher risk for multiple myeloma. According to the Mayo Clinic, one percent of people in the U.S. with MGUS develop multiple myeloma every year.
• Occupational Exposure: Some studies show that exposure to certain chemicals and substances on the job can increase risks for multiple myeloma. Some of these occupations include workers in petroleum industries and agriculture.
• Radiation Exposure: Exposure to radiation may increase the risk of developing multiple myeloma. However, only a small number of cases are linked to radiation.
• Family History: A person with a brother, sister, or parent with multiple myeloma is more likely to develop the disease. According to the American Cancer Society, the risk for a patient with a family history of myeloma is four times greater than someone without a family history of myeloma. However, most people with multiple myeloma do not have any affected relatives.
• Weight: People who are overweight or obese are more likely to develop multiple myeloma. According to the National Cancer Institute, this risk factor is still being studied.

For more information about some of these risk factors, please see the recent related Beacon articles on racial disparities, MGUS, and chemical exposure in multiple myeloma.

Signs and Symptoms »

Multiple myeloma treatments are tailored to patients’ age, general health, lifestyle, goals for treatment, response to any previous treatments, the disease’s stage, and whether the disease is active or inactive.

Smoldering multiple myeloma, also called inactive or asymptomatic multiple myeloma, is a stable form of myeloma where the affected person does not feel any symptoms. In this case, the person may not need treatment. Patients with smoldering multiple myeloma should see their doctors frequently, so that doctors can start treatment if the myeloma progresses to active or symptomatic multiple myeloma.

Patients with active or symptomatic multiple myeloma experience various symptoms, such as kidney problems, hypercalcemia (high levels of calcium in the bone), anemia, and bone damage. There are many treatment options for patients with active myeloma, including induction therapy, radiation therapy, high-dose chemotherapy with stem cell transplants, and maintenance therapy. Some of these options treat symptoms of myeloma, while others directly target the cancerous tumors. Course of treatment is determined on an individual basis and is generally based on a combination of the patient’s age, general health, and symptoms.

Induction Therapy

A patient’s first treatment regimen of chemotherapy drugs is called an induction therapy. The goal of induction therapy is to control the myeloma and reduce any tumors. There are many combinations of drugs that doctors can use to help fight multiple myeloma.

Induction therapies vary depending on whether the patient will receive a stem cell transplant afterward. For those who will not have stem cell transplants, three possible and well-established drug regimens are:

• Melphalan (Alkeran), prednisone, and thalidomide (Thalomid)
• Melphalan, prednisone, and Velcade (bortezomib)
• Revlimid (lenalidomide) and low-dose dexamethasone (Decadron)

However, any individual’s treatment might vary depending on the patient’s unique situation.

Before transplantation, patients routinely receive four rounds of chemotherapy. For these patients, common combinations of drugs used for induction therapy include some of the following: dexamethasone, Revlimid, thalidomide, and/or Velcade. Physicians avoid using melphalan because it interferes with collecting stem cells for the transplant.

Radiation Therapy

Radiation therapy uses high-energy X-rays to kill myeloma cells. Doctors use radiation therapy as a supplement to chemotherapy, to target specific areas that have painful myeloma tumors that are damaging the bone in that area. Unlike some other types of cancer, which deliver the treatment through radioactive “seeds” that are put into the body, myeloma patients receive radiation therapy externally from a machine.

High-Dose Chemotherapy with Stem Cell Transplants

In high-dose chemotherapy with stem cell transplants, doctors use an intense chemotherapy regimen to kill off myeloma cells. Since chemotherapy kills malignant tumor cells as well as healthy cells, patients receive a stem cell transplant to replace healthy bone marrow.

Commonly, the stem cells used in the transplant are the patient’s own. But sometimes, they come from a separate donor. When the stem cells are the patient’s own, the transplant is called an autologous stem cell transplant. A donor transplant is called an allogeneic stem cell transplant.

For autologous stem cell transplants, doctors will collect stem cells from their patients after their induction therapy, but before the high-dose chemotherapy begins. These stem cells usually come from the peripheral blood, or blood that is circulating through the body and are often taken out through the arm. In rare cases, doctors take stem cells directly from patients’ bone marrow. In either case, a doctor may take enough stem cells for two transplants, in case the patient needs a second transplant later.

After stem cell collection, patients undergo the high-dose chemotherapy, usually with high doses of melphalan.

Then, after receiving the high-dose chemotherapy, patients get an infusion of their own previously collected, healthy stem cells through a tube that goes into the chest. The stem cells will migrate through the blood stream into the damaged bone marrow to start producing cells again.

However, when a person receives an allogeneic stem cell transplant, the transplanted cells come from another, closely matched donor: often a healthy family member such as a brother or a sister. In this case, stem cells are not taken from the patient, but taken from the donor when the time for transplantation nears.

Currently, researchers are studying non-myeloablative transplants, sometimes called mini-transplants. Here, the preceding chemotherapy is a lower dose in order to conserve the bone marrow cells prior to treatment. A patient and his or her doctor can try a non-myeloablative transplant in a clinical trial.

Maintenance Therapy

Maintenance therapy is the treatment patients receive after their induction therapy, and after any possible stem cell transplants. The goal of maintenance therapy is to prevent a cancer relapse. Thalidomide is a standard maintenance therapy. Other options include interferons or steroids such as dexamethasone and prednisone.

If the Multiple Myeloma Returns

If the multiple myeloma comes back less than six months after the end of treatment, the patient’s doctor might try the induction therapy again. The doctor might even try another treatment of high-dose chemotherapy with another stem cell transplant.

If it has been more than six months since the first treatment ended, or if patients and their doctors decide to follow a different approach, they may try another drug regimen. Velcade is commonly included in relapse therapy. The time period after relapse is also a common time for patients to try clinical trials. For more information on current clinical trials, please see the National Institutes of Health’s ClinicalTrials.gov.

Supportive Care

Patients get supportive care to treat some of the serious symptoms of multiple myeloma and to relieve pain. Examples of supportive care include bisphosphonates for bone loss and bone pain, antibiotics for infections, radiation therapy for tumors in the bone and bone pain, and chemotherapy for pain.

Prognosis »

Samples of a person’s bone marrow can be tested for different factors that affect prognoses. A lab test called the myeloma cell staging index or plasma cell labeling index can show the percentage of myeloma cells that are growing, with lower labeling indexes indicating a better prognoses.

Labs can also look for creatinine, C-reactive protein, and lactate dehydrogenase in the blood. These molecules are released in higher amounts in the blood when body tissues are damaged. Lower levels of these molecules make for better prognoses.

Another lab test looks at the chromosomes of a myeloma cell to see if there are certain chromosome changes that lead to poorer prognoses. For example, chromosome 13 has a retinoblastoma gene (Rb), which produces proteins that suppress myeloma cell production. However, when this chromosome is missing or defective, it results in a poorer prognosis because the cancerous cells continue to grow; sometimes becoming resistant to treatment.

Furthermore, doctors may use the International Staging System for Multiple Myeloma to determine the outlook for their patients. In this system, myeloma cases are divided into three stages depending on patients’ serum levels of two molecules, beta-2 microglobulin and albumin.

Doctors and scientists have data on the approximate median survival time for patients at each stage of multiple myeloma. Median survival time is the time at which half of the people at that stage have died. These times are counted from when patients begin treatment.

The following table shows the definitions of the different stages of the International Staging System and their associated median survival times. Keep in mind that the data for this table are based on people treated five to 25 years ago. According to the American Cancer Society, modern prognoses for patients getting treated with current techniques are likely to be better than the table shows.

International Staging System Stage Definitions and Median Survival Times