Three studies presented at the American Society of Hematology (ASH) Annual Meeting and Exposition in Orlando support the use of Revlimid as maintenance therapy for multiple myeloma patients.

In two studies, Revlimid (lenalidomide) maintenance increased time to disease progression among multiple myeloma patients after stem cell transplantation.

A third study showed the same benefit for older newly diagnosed multiple myeloma patients who are not candidates for stem cell transplantation.

Side effects were minor across all three studies. However, the researchers did observe the occurrence of secondary cancers in a small number of patients.

Based on intermediate results from these studies, the National Comprehensive Cancer Network added Revlimid maintenance therapy to its multiple myeloma treatment guidelines earlier this year (see related Beacon news).

Revlimid Maintenance After Stem Cell Transplantation (CALGB 100104 Study)

In the first study, referred to as CALGB 100104, 568 multiple myeloma patients under the age of 70 years were randomized to receive either Revlimid maintenance therapy or a placebo following autologous stem cell transplantation.

A preliminary data analysis from this study in 2009 showed such a significant improvement in the time to disease progression in the Revlimid maintenance arm that the study was unblinded, and patients in the placebo arm were allowed to switch over to the Revlimid maintenance arm.

The 18-month follow-up results were presented at the ASH meeting by lead investigator Dr. Philip McCarthy of the Roswell Park Cancer Institute in Buffalo, New York.  The results showed that patients who received Revlimid exhibited a median time to disease progression of 42 months compared to 22 months for patients who received the placebo.

Overall survival was similar for the two groups. Dr. McCarthy explained that this may be due to the significant percentage of placebo patients who switched over to Revlimid maintenance when the trial was unblinded in late 2009.

Patients who received Revlimid were more likely to experience side effects. The most commonly reported side effects included low white blood cell counts, low platelet counts, and bacterial infections.

Dr. McCarthy mentioned that 25 patients, 15 in the Revlimid arm and 10 in the placebo arm, developed a secondary cancer, that is, an additional cancer other than myeloma.  “We can’t say anything specific yet, but we wanted to make sure that people are aware of it,” said Dr. McCarthy.

Twelve-month results were presented at the American Society of Clinical Oncology meeting this summer (see related Beacon news),

Revlimid Maintenance After Stem Cell Transplantation (IFM Study)

In the second study, known as the IFM study, 614 multiple myeloma patients under the age of 65 years who had recently undergone stem cell transplantation, received consolidation therapy with Revlimid, and then were randomized to receive long-term Revlimid maintenance therapy or a placebo.

A preliminary data analysis in late 2009 showed that Revlimid maintenance significantly improved progression-free survival.  Therefore, this trial was also unblinded in mid-2010, and patients who were originally in the placebo group began receiving the Revlimid treatment regimen.

Dr. Michel Attal of the Hopital Purpan in Toulouse, France, and lead investigator of the study presented results at ASH based on data that was collected up until the unblinding of the study. The results showed that Revlimid consolidation therapy improved responses and progression-free survival compared to transplantation alone. Revlimid maintenance therapy, however, did not significantly increase the number of patients who achieved a complete response.

When the study was unblinded, it was estimated that four years after diagnosis 60 percent of patients who received Revlimid maintenance would still be alive without disease progression compared to 33 percent for patients who received the placebo.

This benefit was observed even if patients achieved a complete response after induction therapy, showing the importance of maintenance even if a patient achieves a good response after initial treatment.

Despite the difference in progression-free survival, the overall survival rates for the Revlimid and placebo groups were approximately equal at 83 percent.

Dr. Attal said that longer follow-up is needed to appreciate the impact on overall survival. However, he said that the better progression-free survival is a huge improvement in quality of life. “I’m convinced some of these patients will be cured,” he added.

Dr. Attal described the side effects of Revlimid maintenance therapy as acceptable. The rate of low white blood cell counts was higher in the Revlimid arm of the study, but the rate of blood cots was very low.

Dr. Attal and his colleagues also observed the development of secondary cancers in the study participants. However, he pointed out that the numbers were very low. In the Revlimid group, 16 patients developed secondary cancers compared to three in the placebo group.

Twenty-one percent of patients receiving Revlimid discontinued treatment compared to 16 percent of patients receiving the placebo.

One physician said during the Q&A session following Dr. Attal’s presentation that “Revlimid maintenance is likely to become a new standard of treatment.” Another physician was more skeptical and wanted to see data showing a difference in overall survival between Revlimid maintenance and the placebo arm, since maintenance therapy is associated with side effects and incurs additional cost.

Interim results of the trial were presented at ASCO (see related Beacon news).

Revlimid Maintenance In Newly Diagnosed, Older Myeloma Patients

In the third study, Dr. Antonio Palumbo from the University of Torino in Italy investigated the addition of Revlimid to melphalan and prednisone in elderly newly diagnosed myeloma patients.

The study included 459 patients ages 65 years and older who received one of three possible treatment regimens.  One regimen consisted of nine 28-day cycles of melphalan and prednisone alone followed by placebo (MP).  The second regimen consisted of nine 28-day cycles of melphalan, prednisone, and Revlimid also followed by placebo (MPR).  The third regimen was the same as the second, but, instead of receiving placebo after the first nine cycles of treatment, patients received maintenance therapy with Revlimid (MPR-R).

Dr. Palumbo and his colleagues found that responses were more rapid and better with MPR-R than MP, with a median onset of response of 2 and 3 months, respectively, and overall response rates of 70 percent and 50 percent, respectively.

A comparison of the different regimens showed that the Revlimid maintenance regimen, MPR-R, had a longer progression-free survival than the other two regimens.  Progression-free survival for MPR-R, MPR, and MP were 31, 14, and 13 months, respectively.  These results show a clear benefit to Revlimid maintenance therapy but have caused some physicians to doubt the advantage of using Revlimid upfront in elderly patients.

Side effects of MPR-R were manageable, but a larger percentage of patients on that regimen discontinued therapy due to side effects as compared to patients on MP.  The most common severe side effects were low blood cell counts that occurred during the MPR phase of treatment.

Dr. Palumbo and his colleagues also observed the occurrence of secondary cancers in all three treatment groups. Five cases developed in the MPR-R treatment group, eight in the MPR treatment group, and two in the MP treatment group.

Dr. Palumbo presented earlier interim results at last year’s ASH annual meeting (see related Beacon news).

For more information about these studies, please refer to abstract 37, abstract 310, and abstract 622 on the American Society of Hematology annual meeting website.