In their statement, the experts reviewed the main findings from previous clinical trials that investigated the impact of maintenance therapies containing the novel agents thalidomide (Thalomid), Revlimid (lenalidomide), and Velcade (bortezomib).

Maintenance therapy is a prolonged, and often low-dose, form of treatment given to myeloma patients after their initial therapy. The goal of maintenance therapy is to prevent disease progression for as long as possible while maintaining a favorable quality of life. Maintenance therapy is different from consolidation therapy, which usually involves a shorter course of treatment with the goal of deepening patients’ responses to the initial therapy.

Based on these results, the experts came to the following conclusions for myeloma patients considering maintenance therapy:

The experts did not come to a consensus on the use of Revlimid as maintenance therapy. Revlimid maintenance increased progression-free survival in younger patients, which according to some experts speaks in favor of using Revlimid maintenance. However, Revlimid maintenance was also associated with an increased risk of secondary cancers, which according to some experts cannot be neglected when deciding whether to use Revlimid maintenance. The experts, therefore, said that longer-term survival data is needed before they can make a recommendation in favor, or against, Revlimid maintenance.

The experts stated that thalidomide maintenance is a treatment option for younger patients after stem cell transplantation, since thalidomide maintenance is associated with an increase in progression-free survival. For older patients who are not candidates for stem cell transplantation, the use of thalidomide maintenance is less clear because trial results were mixed in this patient population.

According to the experts, there is currently insufficient evidence available to make specific recommendations for, or against, Velcade maintenance therapy.

Additionally, the experts did not recommend maintenance therapy with interferons or corticosteroids alone.

Revlimid

Summary:

The experts found that Revlimid maintenance is associated with a significant increase in progression-free survival in both younger patients undergoing stem cell transplantation as well as older patients receiving conventional chemotherapy. Results of one study also showed a significant survival benefit with Revlimid maintenance therapy. However, the experts acknowledged that myeloma patients with high-risk chromosomal abnormalities do not benefit from Revlimid maintenance.

However, the experts pointed out that Revlimid maintenance therapy may be associated with an increased risk of secondary cancers (see related Beacon news), which they recommended physicians should bear in mind when deciding whether to prescribe Revlimid maintenance.

If the decision is made to use Revlimid maintenance therapy, the experts recommended a starting dose of 10 mg per day for both younger and elderly standard-risk patients. They added that both continuous therapy, as well as a “three weeks on, one week off” approach, may be effective.

Additional Information:

Results of two clinical trials, the United States CALGB 100104 trial and the French IFM 2005-02 trial, suggest that Revlimid maintenance may be effective in younger, standard-risk myeloma patients who received a stem cell transplant (see related Beacon news).

Results of the CALGB 100104 trial showed that after a median follow-up of 28 months, the median time to disease progression was significantly longer for patients who received Revlimid maintenance than for patients who received a placebo (48 months versus 31 months).

Patients who received Revlimid maintenance also had a significantly longer event-free survival than patients who received a placebo (42 months versus 22 months).

However, they also experienced more cases of low white blood cell counts, low red blood cell counts, low platelet counts, and infections.

Results of the IFM 2005-02 trial showed that after a median follow-up of 36 months, the median progression-free survival was significantly longer in patients who received Revlimid maintenance (41 months versus 24 months). However, the progression-free survival and overall survival were shorter in patients who had high-risk chromosomal abnormalities.

According to the authors of the review, a notable result of both the CALGB 100104 and IFM 2005-02 trials was the increased occurrence of secondary cancers among patients who received Revlimid maintenance.

Last year, after months of controversy over the apparent increase of secondary cancers among myeloma patients receiving Revlimid maintenance, both the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) began safety reviews of Revlimid. The EMA concluded that the benefits of Revlimid continue to outweigh its risks. However, the agency also recommended that the prescribing information for Revlimid be updated with a warning about the risk of new cancers (see related Beacon news).  The FDA investigation is still ongoing.

The experts commented that further studies are needed to evaluate the true risk of secondary cancers to identify risk factors and to develop strategies for their prevention in myeloma patients. According to the experts, “physicians and patients must weigh the benefits of Revlimid maintenance therapy against the low but relevant risk of secondary cancers.”

In addition to the CALGB 100104 and IFM 2005-02 trials, results of an Italian study indicated that Revlimid maintenance also prolongs the progression-free survival of elderly myeloma patients treated with conventional chemotherapy (31 months versus 13 months).

Thalidomide

Summary:

The experts found that thalidomide maintenance after stem cell transplantation may increase progression-free survival and, to a lesser degree, overall survival. However, they pointed out that patients with high-risk chromosomal abnormalities did not benefit from thalidomide maintenance.

The experts added that the lowest active dose of thalidomide is 50 mg per day and that the duration of thalidomide therapy should be limited to one year in order the limit the risk of severe side effects.

For older patients who are not candidates for stem cell transplantation, the experts pointed out that the use of thalidomide maintenance is less clear because trial results were mixed in this patient population.

Additional Information:

Studies of thalidomide maintenance therapy have been primarily in younger patients receiving a stem cell transplant.

In a small number of clinical trials investigating the impact of thalidomide maintenance in elderly patients, roughly half of the patients had been exposed to thalidomide during initial therapy. Results of these trials showed a significant increase in progression-free survival, but not overall survival, in elderly patients treated with thalidomide maintenance (see related Beacon news).

However, the experts were unable to confirm whether elderly patients who had not received thalidomide during initial therapy would benefit more from thalidomide maintenance than patients who had previously received thalidomide.

They indicated that thalidomide maintenance may be a valuable option in standard-risk elderly patients, although elderly patients may not tolerate thalidomide as well as younger patients.

According to the experts, most clinical trials have shown that thalidomide maintenance increases the quality of response and prolongs the progression-free survival of younger myeloma patients (see related Beacon news 1, 2, and 3). Additionally, these trials indicate that the risk for disease progression is similar in patients who received thalidomide during both their maintenance and initial phases and in patients who received thalidomide during their maintenance phase only.

However, the impact of thalidomide maintenance on overall survival rates is not as clear. While some studies indicate that thalidomide maintenance increases overall survival, other studies have shown that thalidomide maintenance fails to provide an overall survival benefit (see related Beacon news).

Therefore, the experts stated that the improved overall survival associated with thalidomide maintenance, as demonstrated in some studies, must be interpreted with caution.

They speculated that the most common explanation for the difference in overall survival rates across studies is the inclusion of elderly patients in some of the thalidomide maintenance trials that showed no improvement in overall survival. Moreover, they commented that differences in the availability of novel agents at relapse across studies may have also contributed to the different overall survival rates of myeloma patients receiving thalidomide maintenance.

In addition, the results of several clinical trials suggest that patients without high-risk chromosomal abnormalities are more likely to benefit from thalidomide maintenance than patients with high-risk factors.

For instance, in the MRC Myeloma IX trial, myeloma patients receiving thalidomide maintenance who did not have high-risk chromosomal abnormalities had a significantly better overall survival than patients who had chromosomal abnormalities.

Velcade

Summary:

The experts acknowledged that specific recommendations cannot be made for Velcade maintenance therapy at the present time because more information is needed regarding the optimal scheduling, dosing, and duration of Velcade maintenance.

They proposed further studies involving patients not previously exposed to Velcade in order to address these issues.

Additional Information:

According to the experts, single-agent Velcade maintenance therapies have only been investigated in myeloma patients who had already received Velcade during initial therapy.

For instance, the HOVON/GMMG clinical trial compared the effectiveness of a Velcade-doxorubicin (Adriamycin)-dexamethasone (Decadron) initial therapy followed by Velcade maintenance (PAD/Velcade) with a vincristine-doxorubicin-dexamethasone initial therapy followed by thalidomide maintenance (VAD/thalidomide).

After 36 months, patients who received PAD/Velcade had significantly better progression-free survival (78 percent versus 48 percent) and overall survival (71 percent versus 42 percent) rates compared to patients who received VAD/thalidomide.

Although the results of the HOVON/GMMG trial showed that Velcade maintenance therapy can be tolerated for up to two years, the experts claimed that the design of the study does not allow for a clear interpretation of the role of Velcade maintenance therapy because patients received different initial therapies.

Other studies have assessed the impact of Velcade maintenance in combination with thalidomide. Two of these studies indicated that Velcade plus thalidomide increases progression-free survival when administered as maintenance therapy.

Chemotherapy, Interferon, And Corticosteroids

Summary:

The results of previous clinical trials have suggested that conventional chemotherapy – melphalan (Alkeran) or BCNU (carmustine) typically used in combination with prednisone – prolongs the duration of remission in myeloma patients initially treated with melphalan plus prednisone. However, the experts pointed out that the use of chemotherapy in maintenance strategies was not pursued further when it was determined that chemotherapy failed to improve overall survival.

Interferon has also been shown to increase the duration of remission in myeloma patients, although results across studies have been mixed. According to the experts, physicians have abandoned the use of interferon in maintenance therapies because of toxicities and the inability to adequately select patients who are likely to benefit from interferon therapy.

Corticosteroids such as prednisone and dexamethasone have also yielded mixed results across studies. While prednisone has been shown to increase remission duration and survival, dexamethasone has been shown to lack benefit in myeloma patients. Taken together, the experts stated that the current data is insufficient to recommend corticosteroid maintenance therapy in myeloma patients.

For more information, please see the IMW consensus statement in the journal Blood (abstract).

Diagnosis Of Kidney Impairment

Kidney impairment affects between 15 and 40 percent of multiple myeloma patients (please see the Beacon series on kidney impairment).

The most common method for assessing kidney function is by measuring the serum level of creatinine, a molecule that the kidneys are supposed to filter from the bloodstream. Patients are diagnosed with kidney impairment if the serum creatinine is higher than 2.0 mg/dL.

Since serum creatinine may depend on a patient’s age, sex, and muscle mass, the International Myeloma Working Group (IMWG) suggested that a more accurate analysis of kidney function may be assessed by the glomerular filtration rate (GFR).  The GFR measures the flow of fluid that is filtered through the kidneys.

Management Of Myeloma Patients With Kidney Impairment

In order to best improve kidney function, the IMWG recommended that myeloma patients with acute kidney failure stay adequately hydrated and receive treatment for potentially elevated serum calcium levels.

Additionally, the group discouraged the use of bisphosphonates (the standard treatment for myeloma bone disease) because they may increase serum calcium levels and further impair kidney function.

Other drugs that should be avoided include intravenous contrast dyes, certain diuretics and antibiotics, and nonsteroidal anti-inflammatory drugs, such as aspirin and ibuprofen.

In the case of severe kidney dysfunction, kidney replacement therapies, such as dialysis or transplant, may be required. The experts advised against plasma exchange as standard procedure for the treatment of kidney failure in myeloma patients. In plasma exchange, parts of the blood plasma are removed, treated, and returned to the patient’s blood circulation.

Treatment With Conventional Chemotherapy

The IMWG confirmed that conventional chemotherapy regimens may result in improved kidney function. In a study of 41 patients, kidney failure was reversed in 73 percent of patients who received treatment with high-dose dexamethasone (Decadron).

The experts recommended treatments containing cyclophosphamide (Cytoxan) or dexamethasone over melphalan (Alkeran)-containing treatment for patients with impaired kidney function because melphalan is primarily excreted by the kidneys. If melphalan is used, dosage should be reduced in patients with kidney impairment.

The group stated that high-dose chemotherapy with melphalan followed by autologous stem cell transplantation is possible in myeloma patients with kidney impairment. However, patients should be under 60 years old and in good health. They recommended that melphalan dosage be lowered from 200 mg/m² to 140 mg/m² in patients with kidney impairment. 

Treatment With Novel Agents

The group stated that the introduction of novel agents, such as Velcade (bortezomib), thalidomide (Thalomid), and Revlimid (lenalidomide), has improved survival rates for myeloma patients with kidney impairment, in some cases even reversing kidney damage.

They found Velcade to be an effective and safe therapy for patients with kidney impairment. Results from a Phase 2 trial demonstrated that 30 percent of patients with kidney impairment responded to Velcade treatment, compared to 45 percent of patients with normal kidney function. A second study suggested that acute kidney failure may be reversed with treatment of Velcade, doxorubicin (Adriamycin), and dexamethasone. Of the 58 patients, 42 responded to treatment, with three of the dialysis-dependent patients no longer needing dialysis.

Based on the available data, the recommended treatment for myeloma patients with kidney impairment is Velcade plus dexamethasone. The IMWG suggested that Velcade be administered at 1.3 mg/m² on days 1, 4, 8, and 11 of a 21-day cycle.

Dexamethasone should be given at a dose of 20 mg on the day of and the day after Velcade administration.

The IMWG also recommended the combination regimen of Velcade, melphalan, and prednisone as a first-line treatment for elderly patients with kidney impairment.

According to the IMWG, clinical trials of thalidomide in patients with kidney impairment have been promising, with one study demonstrating the reversal of kidney failure in 80 percent of patients treated with thalidomide and high-dose dexamethasone.

However, the IMWG cautioned against using thalidomide in patients with kidney impairment since there is limited data from randomized trials.

The IMWG stated that myeloma patients with kidney impairment may be treated with Revlimid.  However, because Revlimid is excreted primarily by the kidneys, reduced dosage is recommended.

Additionally, there is limited data for the efficacy of Revlimid-based regimens in patients with kidney impairment. The majority of Phase 2 and 3 studies with Revlimid exclude patients with serum creatinine levels above 2 mg/dL. However, it has been shown that patients with severe kidney impairment undergoing Revlimid-based treatment experienced an increased frequency of low platelet counts and had shorter overall survival than patients with normal kidney function.

While Revlimid at reduced dosage may be an effective treatment for patients with mild to moderate kidney impairment, the exact dosage is still being determined.

For more information, please read the article in the Journal of Clinical Oncology (abstract).

Over the past decade, the life expectancy of multiple myeloma patients has improved. Currently, most multiple myeloma patients are projected to live 7 to 10 years with good quality of life. Multiple myeloma remains, however, an incurable disease for most patients.

Allogeneic (donor) stem cell transplantation is currently the only treatment option that has the potential to cure multiple myeloma. In donor stem cell transplantation, patients undergo chemotherapy to kill off the myeloma cells and then receive stem cells from a donor to replenish their blood cells.

Despite its therapeutic potential, the use of donor stem cell transplantation is highly debated in the medical field due to the safety risks and rate of relapse. After a stem cell transplant, patients may experience bleeding, infection, and graft-versus-host disease, a complication when transplanted stem cells attack the patient’s body.

In its recently published report, the International Myeloma Working Group (IMWG) made recommendations based on the review of stem cell transplant registries and studies that used several different transplant protocols.

Full Donor Stem Cell Transplants

The IMWG reviewed three transplant registries that contain data on patients who received myeloablative allogeneic (full donor) stem cell transplants. The goal of this type of transplant is to eradicate all myeloma cells before donor stem cells are transplanted into the patient to re-grow new blood cells.

The IMWG also reviewed several clinical trials that compared full donor transplants to autologous transplants. In an autologous transplant, a patient’s own stem cells are collected before intense therapy to kill the myeloma cells, and then the patient’s stem cells are transplanted back afterward. Because the patient’s own stem cells are used in an autologous transplant, it is associated with fewer complications than a donor transplant.

A review of these registries and studies revealed that full donor stem cell transplants were associated with high treatment-related mortality. The lowest reported percentage of treatment-related mortality among these registries and studies was 30 percent, though most groups reported at least 40 percent. The IMWG wrote that a 30 percent or higher mortality rate is “unacceptably high.”

The experts concluded that although myeloablative therapy proved effective for a small percentage of patients, it is not a good option for patients with multiple myeloma who can be treated with autologous stem cell transplantation.

Since treatment-related mortality is improving for full donor stem cell transplants, the IMWG suggested that these transplants could be further studied in well-designed clinical trials.

Reduced-Intensity Donor Stem Cell Transplants

As compared to full donor transplants, the IMWG found that non-myeloablative (also called mini or reduced-intensity conditioning) donor stem cell transplantation, either alone or preceded by autologous transplantation, was associated with a lower treatment-related mortality, as low as 9 percent in two studies. However, patients undergoing the reduced-intensity regimen were twice as likely to relapse (54 percent versus 27 percent).

The IMWG did not find convincing evidence during its review to suggest that donor stem cell transplantation improved survival compared to autologous stem cell transplantation. The group recommended that reduced-intensity donor transplants only be used in clinical trials.

Donor Transplantation In High-Risk Myeloma Patients

Likewise, the IMWG did not find convincing data to support the use of donor stem cell transplantation for patients with high-risk myeloma. However, many of the studies included small numbers of patients.

The IMWG wrote that a full donor transplant may be considered for “exceptional cases” in which the patients are “aware of their unfavorable prognosis and accept the risks of myeloablative conditioning.” The group suggested further studies in patients with chromosomal abnormalities t(4;14), t(14;16), and 17p- as well as patients who do not achieve at least a very good partial response after autologous transplantation.

Improving Donor Transplants

The IMWG stressed that future studies of donor stem cell transplantation be aimed at improving the efficacy and safety of the procedure.

They highlighted the need to better understand the graft-versus-myeloma effect to improve efficacy and the need to better manage graft-versus-host-disease to improve safety.

They also suggested that novel agents, such as thalidomide (Thalomid), Revlimid (lenalidomide), and Velcade (bortezomib), might improve the efficacy of donor stem cell transplantation. They cautioned, however, that the optimal timing and dosage of such protocols has not yet been determined.

For more information, please see the study in the Journal of Clinical Oncology (abstract).

The International Myeloma Working Group identified the following risk factors for patients with smoldering, or asymptomatic, myeloma: the amount of monoclonal protein, the number of bone marrow plasma cells, and the free light chain ratio.

A smoldering myeloma diagnosis is made when monoclonal (M) protein levels are 30 g/l or greater and the proportion of plasma cells in the bone marrow is 10 percent or greater, but there is no associated organ damage.

The International Myeloma Working Group (IMWG) emphasizes that smoldering myeloma must be distinguished from monoclonal gammopathy of undetermined significance (MGUS) because there is a higher risk of progression to multiple myeloma or a related disorder for smoldering myeloma patients.

The frequency of progression to multiple myeloma or a related disease is 10 percent per year in patients diagnosed with smoldering myeloma as compared to 1 percent per year in MGUS patients.

In a previous study, researchers found that five years following a smoldering myeloma diagnosis, 51 percent of patients were predicted to progress to active myeloma or a related disease.  This number increased to 73 percent by 15 years post-diagnosis.

Smoldering Myeloma Risk Factors

In smoldering myeloma, the IMWG identified the amount of the M-protein and the number of plasma cells in the bone marrow as the most important risk factors of disease progression.

In smoldering and multiple myeloma, the M-protein is overproduced by plasma cells and cannot effectively fight infections.

Patients with both 10 percent or greater bone marrow plasma cells and 30 g/l or greater of M-protein were found to be at the greatest risk of disease progression.

Patients with 10 percent or greater bone marrow plasma cells and 30 g/l or greater of M-protein had a risk of disease progression of 87 percent at 15 years, while those with 10 percent or greater bone marrow plasma cells and less than 30 g/l of M-protein had a risk of disease progression of 70 percent at 15 years. Patients with less than 10 percent bone marrow plasma cells and 30 g/l or greater of M-protein had the lowest risk of disease progression (39 percent) at 15 years.

The free light chain ratio was identified as an additional independent factor for disease progression. An abnormal free light chain ratio was associated with higher rates of progression. In healthy individuals and the majority of myeloma patients, an immunoglobulin is composed of two light chains bound to two heavy chains. In some patients, the light chains are separated, creating abnormal “free” light chains in their blood stream.

Abnormal MRI scans of the spine have also been demonstrated to be an increased risk factor for progression.

Smoldering Myeloma Monitoring and Management Guidelines

The IMWG recommends patients have blood and urine analyses done both at the time of diagnosis with smoldering myeloma and two to three months thereafter.  At the time of diagnosis, the IMWG also considers a bone marrow biopsy and a bone scan mandatory procedures.

If the results of initial tests are stable, patients should be monitored every four to six months for a year.  At the end of the year, if results are still stable, evaluation can be extended to once every 6 to 12 months.

Conclusion

Dr. C. Ola Landgren, researcher at the National Institutes of Health and investigator in this study, believes there remains a need to find specific tests to determine which patients will progress to multiple myeloma.

He stated, however, that the guidelines published in the IMWG report “serve as a clinical tool to focus routine labs and clinical work-up on the precursor patients, who, based on crude clinical markers, are more likely to progress. There is no doubt this is a step in the right direction!”

He added, “I truly think there will be a change in the myeloma field during the coming years.  Instead of waiting for the precursor disease to get active and to spread to full-blown multiple myeloma before the doctor will start therapy, I think we will see new targeted treatment concepts, based on molecular profiling/imaging and biologic biomarkers. These strategies will better guide the doctor to start earlier therapy, and they will have abilities to monitor chronic disease management/cure.”

In order to determine specific differences between progressors and non-progressors, Dr. Landgren is conducting a series of studies at the National Institutes of Health on patients with MGUS or smoldering myeloma. He is welcoming patients from around the country to contact Mary-Ann Yancey at  if they are interested in participating in the studies.

For more information, please see the IMWG report (abstract).

The International Myeloma Working Group identified the following risk factors for patients with monoclonal gammopathy of undetermined significance: the amount of monoclonal protein, the type of monoclonal protein, the number of bone marrow plasma cells, and the free light chain ratio.

According to Dr. C. Ola Landgren, researcher at the National Institutes of Health and investigator in this study, approximately three million Americans have a myeloma precursor disease, such as monoclonal gammopathy of undetermined significance (MGUS) or smoldering myeloma, but only about 5 percent will develop multiple myeloma or a related disease.

“At the same time, among those who will develop multiple myeloma, I think there is strong evidence to suggest that they all went through a precursor stage. So, the solution is to identify progressors from non-progressors at an early stage and to deliver intervention (i.e. treatment) that will delay/prevent progression to full-blown disease,” added Dr. Landgren.

With their report, the International Myeloma Working Group (IMWG) aims to help doctors identify which patients may be at a higher risk for disease progression and provide guidelines to help monitor and manage their conditions.

MGUS Rates And Risk Factors

A previous study investigated a group of 21,463 people 50 years and older. The researchers identified 3.2 percent of the people as having MGUS.

The researchers found that the rate of MGUS increased with age.  The condition was more common in men than women, and it was approximately twice as common in African-Americans and Africans compared to Caucasians.  Furthermore, the occurrence of MGUS in first degree relatives with MGUS was higher, suggesting a genetic factor (see related Beacon news).

Of those diagnosed with MGUS, approximately 1.5 percent of patients progressed to multiple myeloma or a related disease each year.

The IMWG identified a number of risk factors to help doctors predict which MGUS patients may progress.

The most important risk factor of progression was the amount of the monoclonal (M) protein at the time of MGUS identification. In MGUS and multiple myeloma, the M-protein is overproduced by plasma cells and cannot effectively fight infections.

In one study, the risk of progression to multiple myeloma or a related disorder 20 years after the recognition of MGUS was 49 percent in patients with an M-protein value of 25 g/l compared to 14 percent for patients with an M-protein value of 5 g/l or less.  MGUS patients with an increase in the amount of the M-protein during the first year after diagnosis were at high risk of disease progression.

The type of monoclonal protein overproduced in MGUS patients was also identified as a risk factor. There are several different types of M-protein.  Each MGUS and myeloma patient overproduces just one type.  Those patients with the IgM or IgA type of M-protein were found to be at increased risk of progression compared to those patients with too much IgG.

Additionally, the IMWG cited a report in which patients with greater than 5 percent bone marrow plasma cells were found to be at increased risk of progression.

Lastly, patients with abnormal free light chain ratios were found to be at significantly higher risk for progression than those with a normal ratio. In healthy individuals and the majority of myeloma patients, an immunoglobulin is composed of two light chains bound to two heavy chains. In some patients, the light chains are separated, creating abnormal “free” light chains in their blood stream.

Among MGUS patients with all of the high-risk factors (M-protein levels greater than 15 g/l, overproduction of IgM or IgA, and abnormal free light chain ratios) 58 percent progressed within 20 years of their MGUS diagnosis. For those with none of these factors present, 5 percent progressed.

MGUS Monitoring and Management Guidelines

The IMWG recommends that when a patient is diagnosed with MGUS, doctors should complete a full physical examination of the patient with emphasis on symptoms that may suggest multiple myeloma.

If blood work shows that the serum M-protein is low and of the IgG type and that the free light chain ratio is normal, patients should be categorized as low risk.  In this scenario, patients should be monitored again in six months and, if stable, followed every two to three years until symptoms of multiple myeloma or a related disease appear.

If a patient with MGUS has a high M-protein level of IgA or IgM type and an abnormal free light chain ratio, the IMWG recommends a bone marrow biopsy be conducted to rule out multiple myeloma or a related disease.  If results do not indicate an underlying plasma cell disorder, patients are considered intermediate or high risk.  These patients should be monitored again in six months and then annually until symptoms of multiple myeloma or a related disease appear.

For more information, please see the IMWG report (abstract).

“Very good partial response” is one of the terms defined by the International Myeloma Working Group (IMWG) to categorize how patients respond to treatment. According to IMWG criteria (see related Beacon news), patients reach very good partial response when the level of abnormal “M” proteins in their blood decreases by 90 percent.

Previous studies evaluating high-dose chemotherapy have shown that major tumor reduction as indicated by at least very good partial response is associated with increased progression-free and overall survival. In this study, researchers further examined the relationship between very good partial response and long-term prognosis.

Researchers analyzed the data of patients who participated in the 1999 trials conducted by Intergroupe Francophone du Myelome (IFM 99-02 and 00-04). In both trials, patients received a combination induction therapy of vincristine (Oncovin), doxorubicin (Adriamycin), and dexamethasone (Decadron), known as VAD.

Of the 680 patients evaluated for response to induction, 27 (4 percent) achieved complete response, 81 (12 percent) reached very good partial response, 337 (50 percent) achieved partial response, and 235 (34 percent) experienced less than partial response.

Next, patients underwent double autologous stem cell transplants, in which their own previously-collected stem cells were transplanted back into their bloodstream. Of the 802 patients included in the analysis, 445 (55 percent) achieved at least very good partial response, 288 (36 percent) reached partial response, and 69 (9 percent) experienced either stable disease or disease progression. The median follow-up time was 67 months.

Researchers observed that event-free survival – the time passed without disease progression, relapse, or death – was significantly longer in patients who had very good partial response or better than in those who achieved partial response (42 months versus 32 months, respectively). This translated into a five-year event-free survival rate of 34 percent in VGPR-or-better patients versus 26 percent in patients with partial response. Patients with very good partial response also experienced significantly greater five-year overall survival rate (74 percent versus 61 percent).

Researchers determined that as a single factor, partial response or less is an indicator of a shorter event-free and overall survival. Based on their results, researchers concluded that achieving very good partial response should serve as a major treatment goal for patients and their physicians – not only does it correlate with better short- and long-term event-free and overall survival, but it also encapsulates a larger population of patients than complete response.

For more information, please see the Journal of Clinical Oncology (abstract).