Lenalidomide (Revlimid) dramatically reduced the rate of recurrence in patients with multiple myeloma (MM) following first-line autologous stem cell transplant (ASCT), according to interim results of a phase III study. The data were presented at the 2010 ASCO Annual Meeting by lead investigator Michel Attal, MD, of Purpan Hospital in Toulouse, France, speaking for the Intergroupe Francophone du Myélome.¹

Despite the use of autologous transplant in patients with MM, residual disease is typically present and almost all patients will eventually relapse. Thus far, maintenance treatment has had limited effectiveness, with thalidomide (Thalomid) showing the most promise. However, its activity has been curtailed by cumulative toxicity, including peripheral neuropathy.

"An interim analysis of our study suggests that lenalidomide may be the first effective maintenance therapy for MM," said Dr. Attal.

Lenalidomide is an oral analog of thalidomide, with less toxicity. The drug is FDA-approved as second-line treatment of MM and myelodysplastic syndromes. The present study sought to compare lenalidomide maintenance therapy vs placebo in patients who have undergone first-line ASCT. The study enrolled 614 patients under the age of 65 years with nonprogressive MM up to 6 months after first-line ASCT. All patients received consolidation therapy with oral lenalidomide at 25 mg/d on days 1 to 25 every 28 days for 2 months. One group was randomized to maintenance therapy with lenalidomide, 10 to 15 mg/d until relapse, or placebo.

Study Data

Patients in both groups had similar demographic and disease characteristics at baseline. Patients were stratified according to level of response to ASCT, ß₂-microglobulin, and chromosome 13 deletions prior to consolidation therapy.
At a median follow-up of 24 months from randomization, maintenance therapy was superior, so the study was unblinded, Dr. Attal said. Consolidation therapy with lenalidomide improved the rate of very good partial responses to about 70%-about 10% higher than after ASCT, he noted.

At 3 years, progression of disease or death occurred in 77 of the 307 patients assigned to maintenance lenalidomide (25%) vs 143 of the 307 placebo-treated patients (47%). Median progression-free survival (PFS) has not yet been reached in the maintenance therapy arm but was 24 months in the placebo arm. The 3-year progression-free survival (PFS) rate was 68% in the group treated with maintenance lenalidomide vs 34% in the placebo group-a 54% difference that was highly statistically significant (P < 10^-7). PFS results were consistent across predefined subgroups for response to ASCT, ß₂-microglobulin, and chromosome 13 deletion.

At the first preplanned interim analysis, maintenance therapy was well tolerated, with a low discontinuation rate due to adverse events and no grade 3 or 4 neuropathy, Dr. Attal said.

The fact that no significant differences in response were seen between the two groups after maintenance therapy indicated "a true maintenance effect," according to Dr. Attal.

Philip McCarthy, MD, of the Roswell Park Cancer Institute in Buffalo, NY, presented the CALGB data at the 2010 ASCO Annual Meeting.² ■

References

1. Attal M, Cristini C, Marit G, et al: Lenalidomide maintenance after transplantation for myeloma ( abstract 8018). Presented at the 2010 ASCO Annual Meeting, Chicago, June 6, 2010.

2. McCarthy PL, Owzar K, Anderson KC, et al: Phase III intergroup study of lenalidomide versus placebo maintenance therapy following single autologous stem cell transplant (ASCT) for multiple myeloma (MM): CALGB 10014 ( abstract 8017). Presented at the 2010 ASCO Annual Meeting, Chicago, June 6, 2010.