Because of its effectiveness, the combination of Revlimid and dexamethasone (RD) has become a standard treatment option for patients with relapsed or refractory myeloma. However because Revlimid cannot be broken down effectively by the liver, it circulates throughout the body until it is filtered by the kidneys to be excreted in the urine.

Approximately 20 percent of multiple myeloma patients develop kidney failure, and in 2009, the US Food and Drug Administration (FDA) announced a revision to Revlimid’s prescribing information, warning patients with impaired kidney function to reduce their dosage of Revlimid accordingly (see related Beacon news).

In their study, researchers evaluated the effectiveness of RD therapy in patients with impaired kidney function. Kidney function is assessed by determining how quickly the kidneys filter creatinine, a waste product produced by the muscles. In this study, researchers defined impaired kidney function as creatinine clearance of less than 50 mL/minute.

Researchers recruited 50 patients with relapsed or refractory myeloma who had undergone a median of two therapies prior to the study. Patients were treated with 28-day cycles of Revlimid (days 1 to 21) and dexamethasone (40 mg on days 1 to 4 and 15 to 18 during the first four cycles and on days 1 to 4 from cycle 5 on).

In accordance with FDA safety guidelines, the dosage of Revlimid each patient received was determined based on their creatinine clearance. Patients with normal kidney function, defined in this study as a clearance of 50 mL/minute or greater received the standard dose of 25 mg per day.

Twelve participants (24 percent) had impaired kidney function at the start of the study. Patients with moderate kidney impairment (30 mL/minute to <50 mL/minute) received 10 mg of Revlimid per day. The three patients with severe kidney impairment (<30 mL/minute) who were not on dialysis received 15 mg every other day, and one patient on dialysis was given 15 mg three times a week.

Among the 50 participants, 16 (32 percent) achieved partial response, seven (14 percent) reached very good partial response, and seven (14 percent) complete response, for an overall response rate of 60 percent. There was no difference in overall response between patients with normal kidney function and patients with impaired kidney function (60.5 percent versus 58 percent).

Patients experienced remission for a median of 9 months and overall survival for a median of 16 months. Impaired kidney function did not result in any difference in progression-free and overall survival.

The most common side effects included a reduced white blood cell count (28 percent), fatigue (16 percent), infection (14 percent), a reduced platelet count (1o percent), diarrhea (2 percent) and blood clots in the body’s deep veins (2 percent). Once again, having reduced kidney function did not increase the occurrence of side effects.

Among the 12 patients with impaired kidney function, three achieved complete kidney response, defined as an increase in creatine clearance to 60 mL/minute or greater. Two experienced minor kidney response, defined as a 15 mL/minute to <30 mL/minute increase in the creatinine clearance of someone who has severe kidney impairment.

Researchers concluded that adjusting Revlimid dosage according to kidney function results in the same rate of response and does not negatively impact progression-free and overall survival or rate of side effects. Furthermore in some cases, the Revlimid-dexamethasone therapy improved kidney function. They recommended further studies examining RD therapy’s effectiveness in patients with severe kidney function and as an agent for improving kidney function.

For more information, please see the European Journal of Haematology (abstract).

Researchers had previously found that Velcade resulted in a better response rate, time to progression, and overall survival compared to dexamethasone in relapsed/refractory myeloma patients. Based on these results, Velcade has become one of the standard treatments for relapsed/refractory myeloma patients.

Previous trial results had also shown that Velcade kept its superiority compared to dexamethasone irrespective of the number of prior therapies. However, the effect of specific prior therapies on outcome had not been examined prior to this recent study.

Researchers therefore conducted a subgroup analysis of previous trial results to determine if certain prior therapies, specifically thalidomide and ASCT, influenced Velcade’s efficacy relative to dexamethasone in relapsed/refractory myeloma patients.

In their analysis, the researchers found that none of the prior therapies, including thalidomide and ASCT, influenced Velcade’s superior efficacy compared to dexamethasone.

However, the researchers confirmed previous findings that patients with prior thalidomide treatment had a lower response rate, shorter time to progression, and decreased overall survival after Velcade treatment than patients not treated with thalidomide. The same effect was observed in patients treated with dexamethasone. Further analysis showed that these differences were independent of disease stage, the patient’s response to treatment, or the number of prior treatments.

The researchers also found that ACST patients experienced a higher overall response rate after Velcade treatment compared to patients who did not receive ASCT. They attribute this finding to common selection criteria for ASCT patients, such as youth and high response to treatment. ASCT patients also initially exhibited lower b2-microglobulin and high albumin levels, which are indicators of a positive prognosis.

Patients who received an ASCT and then entered the clinical trial after their first relapse exhibited the best response to Velcade compared to other subgroups, with an overall response rate of 48 percent, a complete response rate of 6 percent, and median time to progression of seven months. 

The researchers suggested that further research is needed to determine the optimal treatment sequence for Velcade and other effective treatments in relapsed/refractory myeloma patients.

For more information, please see the report in the British Journal of Haematology (abstract).

ImmunoCellular Therapeutics To Receive Patent For ICT-69 – On March 2, ImmunoCellular Therapeutics, a biotechnology company that is developing immune-based therapies for cancer treatment, announced that it received a Notice of Allowance on its patent application for ICT-69, a monoclonal antibody that targets multiple myeloma and ovarian cancers. Generally, this notification means that a patent will be issued once the issue fee is paid. For more information, see the ImmunoCellular Therapeutics Web site.

Myeloma Awareness Month Teleconference Series – There are three more teleconferences in the International Myeloma Foundation (IMF) teleconference series celebrating March as Myeloma Awareness Month. Patients, family members, caregivers, and health care professionals are welcome to join. The teleconferences provide up-to-date information regarding multiple myeloma and are held each Friday during March at 7 p.m. EST. Each teleconference will include an hour-long presentation followed by a 30-minute Q&A session on education (March 12), research (March 19), and advocacy (March 26). Please see the IMF Web site for more information.

Living With Myeloma Conference – The Arizona Myeloma Network is hosting its fourth annual “Living With Myeloma” conference on March 27 from 8:30 a.m. to 4:30 p.m. at the Scottsdale Conference Center. Physicians and researchers, including Dr. Robert Kyle, Professor of Medicine at the Mayo Clinic, will be giving invited talks. Patients, family members, caregivers, physicians, researchers, and health care providers interested in myeloma are invited. The conference, including a continental breakfast and hot lunch, is free. Heath care professionals may receive 4.5 continuing medical education credits for attending. Space is limited for the conference, and those interested in attending are urged to register quickly. For registration and more information, visit the Arizona Myeloma Network Web Site.

For a more detailed listing of myeloma related events, please check the Myeloma Beacon Events Calendar.

Following diagnosis with multiple myeloma, the average survival time varies based on the type of treatment that a patient receives. For patients treated with high-dose chemotherapy and autologous transplantation, the average survival time is five to seven years. The majority of these patients are younger than 65 years old. Patients treated with conventional chemotherapy have an average survival time of three to four years. Many of the patients who are treated with conventional chemotherapy are older than 65.

In their study, researchers evaluated patient demographics and clinical data from 10,549 myeloma patients. The majority of patients (84 percent) were at least 50 years old. Sixty-six percent of patients received conventional chemotherapy as a first-line treatment, and 34 percent received high-dose therapy with autologous transplantation. Survival time was calculated from the time of diagnosis.

Researchers found a significant association between age and the classification of a patient’s disease stage, according to the International Staging System (ISS). Higher age was linked to a more advanced ISS stage.

The median survival time for all participants was 3.7 years; this observation did not differ significantly between male and female participants. However, the survival time steadily decreased as the age of the patients increased. In patients diagnosed with myeloma when they were 40 years old or younger, the median survival time was 5.1 years. The median survival time was 5.0 years for patients ages 40 to 49; 4.3 years for patients age 50 to 59; 3.3 years for patients ages 60 to 69; 2.6 years for patients ages 70 to 79; and 1.9 years for patients aged 80 years and older.

Researchers also compared the life spans for myeloma patients versus people not diagnosed with myeloma by using average life expectancy data that was adjusted for age, sex, year of diagnosis, and nationality. For all patients in the study, the average life span was 16.8 years less than the average life span for a patient without myeloma. This finding is significantly higher than the average difference in life span for patients diagnosed with all cancers (12.5 years).

The difference in life spans between myeloma patients versus people not diagnosed with myeloma decreased as the patient’s age increased. For patients diagnosed with myeloma when they were 40 years old or younger, the average lifespan was 36.1 years less than the average life span for a patient without myeloma.   The lifespan difference was 26.9 years for patients ages 40 to 49; 19.9 years for patients age 50 to 59; 13.7 years for patients ages 60 to 69; 8.1 years for patients ages 70 to 79; and 4.6 years for patients aged 80 years or older. The authors of the study suggest that this pattern is expected because the relatively short survival time of myeloma patients amounts to a greater difference in lifespan between patients and non-patients in younger age groups.

The results also revealed that patients ages 40 to 59 who were treated with high-dose chemotherapy and autologous transplantation had a greater survival time (by about two years) than patients of the same age groups treated with conventional chemotherapy. This increased survival time was not found in patients in other age groups. The authors hypothesize that patients between 40 and 59 years of age benefit most from high-dose chemotherapy and autologous transplantation, compared to patients in other age groups. However, the authors noted that this result is limited because the findings are non-randomized and retrospective.

The authors of the study conclude that age is an important risk factor for survival in multiple myeloma. Although the survival time for patients declines with age, the authors suggest that the widespread use of novel therapeutic agents (such as thalidomide [Thalomid], Velcade [bortezomib], and Revlimid [lenalidomide]), may lead to extended survival times.

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

Researchers also discovered that prior treatment with thalidomide (Thalomid) was associated with a decreased progression-free and overall survival.

Multiple myeloma patients with the chromosomal abnormalities del(13), t(4;14) or del(17p) are associated with a poorer prognosis in response to traditional chemotherapy. However, new drug and treatment options have the potential to overcome this poor prognosis. In particular, the relatively new combination of Revlimid and dexamethasone (RD) has proven highly effective in treating patients with relapsed or refractory myeloma.

Studies examining whether the RD combination can overcome the disadvantages associated with genetic risk factors like del(13), t(4;14), and del(17p) have given mixed results. In this retrospective study, researchers evaluated the impact of genetic risk factors and prior treatment on patient outcome in response to the RD combination therapy.

Researcher collected the medical records of 207 relapsed and refractory myeloma patients who had been treated with Revlimid and dexamethasone. Patients received a median of five 28-day cycles of Revlimid (25 mg/day on days 1 to 21) and dexamethasone (40 mg/day on days 1 to 4, 9 to 12, and 17 to 20 during cycles 1 to 4; days 1 to 4 from cycle 5 on).

Prior to Revlimid-dexamethasone therapy, patients had undergone a median of three treatments with drugs such as Velcade (bortezomib), thalidomide, or high-dose melphalan (Alkeran). Researchers also determined how many patients had genetic risk factors. Out of 191 patients tested for del(13), 41 percent had the abnormality. Out of the 184 patients tested for t(4;14), 14 percent had the abnormality, and seven percent of the 120 patients tested for del(17p) had the abnormality.

The overall response rate (ORR), defined as the rate of people achieving partial response or better, was 59 percent. Fourteen percent of patients reached very good partial response and seven percent showed a complete response. The median remission duration was 9.6 months, and the median overall survival was 15.1 months.

In patients with del(13), the overall response rate was significantly lower in comparison to patients without the risk factor (43 percent versus 71 percent). Median progression-free and overall survival were also significantly shorter (PFS: 5.0 months versus 12.5 months; OS: 10.4 months versus 17.4 months).

The same pattern was observed in patients with t(4;14). Patients with t(4;14) experienced a 39 percent overall response rate, a 5.5-month remission duration, and a 9.4-month overall survival’ whereas patients without t(4;14) had a 62-percent ORR, a 10.6-month PFS, and a 15.4-month OS.

There were too few del(17p) patients to perform a meaningful statistical analysis.

In terms of treatment history, patients who had previously been treated with Velcade had significantly lower overall response rates to the RD combination than those who had not (55.4 percent versus 74.3 percent). They also experienced shorter median progression-free survival (8.3 months) and overall survival time (12.2 months). In patients who had no prior Velcade history, median progression-free and overall survival periods had not been reached yet.

While no difference was observed between patients with thalidomide history and those without, researchers discovered that patients who had progressed after thalidomide treatment had a shorter progression-free and overall survival than those who had not progressed (PFS: 5.7 months versus 15.7 months; OS: 9.7 months versus 16.1 months).

The researchers determined that the del(13) abnormality could be used to predict overall response and remission duration, with the presence of del(13) correlating with lower response rates and shorter progression-free survival. The number of prior therapies a patient had undergone also proved to be a predictor of overall response rate, with more prior therapies correlating with lower response rates. They added that progression during thalidomide therapy may be a predictor of a shortened overall survival and reduced response duration.

For more information, please see the journal Leukemia (abstract).

The update provides a fuller, long-term picture of the advantages of some of the autotransplant regimens being tested. It represents the first international effort at systematically updating previously reported trial results, which had indicated that autotransplantation with high-dose melphalan (Alkeran) therapy significantly extends the survival of multiple myeloma patients.

Autologous stem cell transplantation, or autotransplantation, is a common treatment option for newly diagnosed myeloma patients. Stem cells are collected from the patient before chemotherapy and then transplanted afterward to replace the stem cells destroyed during the chemotherapy treatment.

“Given the fortunately extended survival now enjoyed by many myeloma patients, it is critical to provide long-term follow-up analyses as done in this paper,” said Dr. Bart Barlogie, lead author of the paper.

The report updated the results for eight autotransplantation trials. The trials are summarized in the table below:

Following up on these studies resulted in several important observations.

Increased survival in newer trials. The 10-year overall survival estimates increased in more recent trials, from 20 percent to 30 percent in IFM90, IFM94, S9321, and TT1.

New longer-term information on thalidomide use. Although the original results from IFM9902 noted a survival benefit with thalidomide maintenance therapy, the longer follow-up could not confirm these findings. Dr. Barlogie said that it is currently not fully understood why the initial observations, though statistically significant, did not hold up over time.

However, this long-term follow-up study uncovered that patients who received TT2 experienced significant survival improvement with thalidomide induction therapy, though this was noted almost eight years after the trial and after 80 percent of patients had discontinued its use. It is not yet known why the survival benefit of thalidomide in TT2 was not observed for so long, but this delay has also been observed with high-dose glucocorticoid therapy in an acute form of pediatric lymphoblastic leukemia.

Dr. Barlogie, who leads the research group that conducted the original TT2 trial, speculated that thalidomide may be particularly effective at the start of therapy, resulting in a survival benefit. In order to compare the efficacy of the thalidomide-based treatment versus the control, Dr. Barlogie’s group plans on examining bone marrow samples from patients in both treatment groups obtained periodically over the first year of treatment.

Better survival rates for some trials over others. Researchers also analyzed the eight trials using four variables that independently affect overall survival: albumin, B2M, LDH, and hemoglobin levels. They observed superior survival rates for the TT2, TT3, and IFM9902 trials, compared to the other five trials; for tandem transplantations, compared to both single transplantations and standard therapies; and for tandem transplantations with thalidomide, compared to trials without thalidomide.

The authors of the study concluded that longer follow-up is needed in order to fully appreciate the collective impact of successful therapeutic interventions. Although the current paper only updated the results of three research groups, the authors encourage other groups to follow their lead.

In order to have a complete understanding of the survival effects of therapeutic trials, Dr. Barlogie recommended that clinical trial participants be followed for the rest of their lives.

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

In their study, researchers randomly assigned 556 patients to receive three cycles of either vincristine (Oncovin), doxorubicin, and dexamethasone [VAD] or thalidomide, doxorubicin (Adriamycin), and dexamethasone (Decadron) [TAD] as induction therapy. All patients received high-dose melphalan (Alkeran) with an autologous stem cell transplant, followed by maintenance therapy with either alpha-interferon for patients who received VAD or thalidomide for patients who received TAD. Alpha-interferon are naturally occurring proteins that improve the body’s response to infection and slow tumor growth.

The use of thalidomide significantly improved the overall response rate both before and after high-dose therapy with melphalan. For patients who received thalidomide as maintenance, 88 percent achieved at least a partial response, compared to 79 percent of patients who received alpha-interferon as maintenance.

The quality of the response also improved with thalidomide-based induction and maintenance. For patients who received thalidomide as maintenance, 66 percent achieved a very good partial response, compared to 54 percent of patients who received alpha-interferon as maintenance.

Furthermore, the median event-free survival (EFS) – the length of time after treatment that a patient does not experience a complication of myeloma – for patients randomized to thalidomide was 34 months, compared to 22 months for patients who did not receive thalidomide. The median progression-free survival (PFS) – the length of time after treatment that a patient does not experience disease progression – for patients randomized to thalidomide was 34 months, compared to 25 months for patients who did not receive thalidomide.

Although thalidomide improved overall response rates and extended EFS and PFS, it did not result in a statistically significant lengthened overall survival time because patients randomized to thalidomide experienced shorter median survival times after progression/relapse (20 months) than patients who did not receive thalidomide as induction or maintenance therapy (31 months).

The authors of the study hypothesized that this may be due to the discrepancy in the usage of thalidomide after progression/relapse – 64 percent of refractory/relapsed patients from the VAD regimen received thalidomide during salvage therapy, while only 38 percent of patients with progression/relapse from the TAD regimen received salvage therapy with thalidomide.

The study authors also presented an alternate explanation, in which aggressive drug-resistant clones may have generated relapses after prolonged exposure to thalidomide.

The overall results suggest that the use of thalidomide as induction and maintenance therapy is a promising approach for treatment of myeloma. However, it is not yet known how prior exposure to thalidomide as induction therapy impacts its efficacy as maintenance therapy. The authors of the study propose that thalidomide should only be prescribed for a limited duration as post-induction therapy to avoid a relapse caused by resistance to the drug. 

For more information, please see the study in the journal Blood (abstract) or the clinical trial description.

To highlight the most important of these studies, the Myeloma Beacon surveyed leading physicians and researchers in the field. These physicians and researchers were asked to name the three peer reviewed journal articles published in 2009 and the three conference abstracts from 2009 that have the most important findings or implications relating to multiple myeloma.

The top three journal articles and conference abstracts that they chose are presented below.

Journal Articles

1: Pomalidomide Shows Remarkable Activity In Myeloma

According to the physicians surveyed, the most important study published in 2009 evaluated a combination of pomalidomide (Actimid, CC-4047) and low-dose dexamethasone (Decadron) in relapsed and refractory myeloma patients. In the study, 63 percent of patients, many of whom had been resistant to thalidomide (Thalomid), Revlimid (lenalidomide), and Velcade (bortezomib), responded favorably to the treatment.

The study confirmed earlier results indicating that pomalidomide is the most potent drug of its kind, a class of molecules, known as immunomodulatory agents, that includes thalidomide and Revlimid.

For more information, please see the Journal of Clinical Oncology (abstract) and the related Beacon news article.

2: MGUS Always Precedes Multiple Myeloma

In second place, a prospective study analyzed the blood samples taken from myeloma patients before their diagnosis. Researchers learned that in nearly every case, the patients had monoclonal gammopathy of undetermined significance (MGUS), a blood disorder present in three percent of Americans over the age of 50.

According to Dr. S. Vincent Rajkumar, a professor of medicine at the Rochester, Minnesota, Mayo Clinic and an author on the paper, the study’s findings settle a long-standing debate on whether MGUS is a consistent predecessor to myeloma. Researchers can now focus on identifying factors that increase the risk of MGUS progression.

“By studying mechanisms that are associated with progression, we will [ultimately] be able to develop earlier therapies that can be used to delay or prevent myeloma from happening,” wrote Dr. Ola Landgren, an investigator at the National Cancer Institute and lead author of the study, in an email to the Beacon.

For more information, see the journal Blood (abstract) and the related Beacon news article.

3: Maintenance Therapy After Transplantation Prolongs Life Expectancy

In a tie for third place is a study evaluating the post-transplantation benefits of either prednisone or a combination of prednisone and thalidomide, for patients treated with thalidomide and an autologous stem cell transplant. Patients in the combination therapy group experienced a longer remission duration and overall survival.

For more information, see the Journal of Clinical Oncology (abstract) and the related Beacon news article.

3: Very Good Partial Response Is A Good Indicator of Long-Term Outcome

The other third place study examined how patient response to treatment was associated with event-free and overall survival. Researchers followed up with patients who had undergone an autologous stem cell transplant for a median of 67 months. They discovered that patients who achieved very good partial response or better had significantly longer event-free and overall survival.

Based on their results, researchers recommended that very good partial response should become the standard treatment goal for patients since it is more attainable than complete response, yet offers similar benefits in event-free and overall survival.

For more information, see the Journal of Clinical Oncology (abstract) and the related Beacon news article.

Conference Abstracts

1: Velcade Treatment Options In Elderly Patients With Newly Diagnosed Myeloma

The surveyed physicians voted as most important a study presented at the American Society of Hematology (ASH) conference in early December in which researchers compared an induction therapy combination of Velcade, thalidomide and prednisone (VTP) with the already-popular regimen of Velcade, melphalan (Alkeran), and prednisone (VMP) in newly diagnosed elderly patients. Both treatments proved to be equally and highly effective.

Researchers also compared maintenance therapies of Velcade-thalidomide (VT) and Velcade-prednisone (VP), both of which improved patient responsiveness to the point of overcoming negative genetic risk factors.

For more information, please see ASH abstract 3 and the corresponding Beacon news article.

2: Revlimid Treatment Options In Elderly Patients With Newly Diagnosed Myeloma

For second place, the surveyed physicians chose a Phase 3 trial presented at the ASH conference that investigated Revlimid’s effectiveness as both an induction and maintenance therapy. Patients treated with a combination of melphalan, prednisone, and Revlimid followed by Revlimid maintenance had a decreased risk of disease progression than patients treated with melphalan and prednisone followed by a placebo.

Final results of the study are expected at the American Society of Clinical Oncology meeting later this year. The study’s findings offer substantial support for Celgene as it applies for FDA approval of Revlimid as a first-line treatment option in multiple myeloma.

For more information, please see ASH abstract 613 and the corresponding Beacon news article.

3: VMPT Effectively Treats Elderly Patients With Newly-Diagnosed Myeloma

In a tie for third place, another ASH conference study investigated the impact of adding thalidomide to the standard regimen of Velcade, melphalan, and prednisone (VMP). Patients treated with VMPT had a greater response rate than those treated with VMP, but they also encountered more blood-related side effects.

“VMPT represents the next generation,” wrote Dr. Antonio Palumbo, chief of the myeloma unit at the University of Torino in Italy and lead author of the study, in an email to the Beacon. “[The four drugs] improve response and progression-free survival with a higher toxicity, but this is [still] the first schema that is superior to VMP.”

For more information, please see ASH abstract 128 and the corresponding Beacon news article.

3: Elotuzumab Combination Produces Encouraging Results In Multiple Myeloma

Also tied for third place is another ASH presentation that provided positive results about the effectiveness of elotuzumab in combination with Revlimid and low-dose dexamethasone at treating multiple myeloma. The combination therapy led to a 92 percent response rate from patients, with manageable side effects.

A new antibody, elotuzumab targets proteins that are unique to myeloma cells and causes the cells to die.

“This is an important study because it represents the first evidence that an antibody can have efficacy in myeloma, and it confirms the suggestion that Revlimid enhances immunity and thus enhances the efficacy of an immune-mediated agent like elotuzomab,” wrote Dr. Sagar Lonial, an associate professor at Emory University’s School of Medicine and lead author of this study, in an email to the Beacon.

A multinational continuation of the trial is currently recruiting patients. For more information, please see the clinical trial description, ASH abstract 432, and the corresponding Beacon news article.

The Myeloma Beacon would like to thank the physicians who participated in the survey for their assistance and expertise:

S. Vincent Rajkumar, M.D.
Mayo Clinic, Rochester, MN

Sundar Jagannath, M.D.
St. Vincent’s Comprehensive Cancer Center, New York, NY

Sagar Lonial, M.D.
Winship Cancer Institute
Emory University School of Medicine, Atlanta, GA

Antonio Palumbo, M.D.
University of Torino, Italy

Jesus F. San Miguel, M.D.
University of Salamanca, Spain

“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).

Myeloma Awareness Month Teleconference Series – Each Friday during the month of March, the International Myeloma Foundation (IMF) will be hosting a teleconference to raise awareness and provide up-to-date information about multiple myeloma. The teleconferences are scheduled for 7 p.m. EST and will include a 60 minute presentation followed by a 30 minute Q&A. Patients, family members, caregivers, and health care professionals are welcome to join. Please see the IMF Web site for more information.

NCI Designs MGUS/Smoldering Myeloma Study – Researchers from the National Cancer Institute (NCI) are in the process of developing a prospective study with the goal of identifying causes of transformation from monoclonal gammopathy of undetermined significance (MGUS) and smoldering myeloma (both asymptomatic, pre-malignant disorders) to multiple myeloma. The study will enroll 350 patients with MGUS or smoldering myeloma in the United States and follow them for up to five years. For more information, please contact the research nurse for this study, Mary Ann Yancey, at (301) 435-9227 or yanceym@mail.nih.gov.

For a more detailed listing of myeloma related events, please check the Myeloma Beacon Events Calendar.