ATLANTA—Combination therapy with lenalidomide (Revlimid) plus dexamethasone(Drug information on dexamethasone) (Len/Dex) appears to provide a survival advantage over dexamethasone alone in patients with relapsed or refractory multiple myeloma, according to a study presented at the 2005 annual meeting of the American Society of Hematology (abstract 6). "Lenalidomide is a novel, orally administered, immunomodulatory drug that has single-agent activity against multiple myeloma, and it has additive effects when combined with dexamethasone," said Meletios Dimopoulos, MD, of the University of Athens School of Medicine, Athens, Greece.
To investigate the efficacy of a Len/Dex combination, Dr. Dimopoulos and investigators in the Lenalidomide MM-010 Study Group evaluated Len/Dex vs Placebo/Dex in 351 patients from Europe, Australia, and Israel with refractory or relapsing multiple myeloma. A related trial, MM-009, is evaluating the same regimen in 354 patients in the United States and Canada.
All patients in the current study received dexamethasone 40 mg on days 1-4, 9-12, and 17-20. Patients were randomized to also receive placebo (n = 175) or 25 mg lenalidomide (n = 176) on days 1-21. A total of four 28-day cycles were completed. Patients in the two arms were well matched. Median time from diagnosis was 4.2 years in the Len/Dex arm and 4.8 years in the Placebo/Dex arm. Among all patients, prior therapies included dexamethasone (67%), thalidomide(Drug information on thalidomide) (Thalomid) (34%), stem cell transplantation (55%), and bortezomib(Drug information on bortezomib) (Velcade) (4%).
The overall response rate was significantly superior with Len/Dex vs Placebo/Dex (59% vs 24%; P < .001). Outcomes were superior in terms of proportion achieving complete response (17% vs 4%; P < .001) and partial response (42% vs 20%; P < .001). Patients in the combination arm also demonstrated significantly superior median time-to-progression (11.3 vs 4.7 months; P < .001).
"We were very impressed to see that both MM-010 and MM-009 showed identical results even though they were conducted in different parts of the world," Dr. Dimopoulos said. While data on overall survival are not yet available for the MM-010 study, results from the North American MM-009 study have shown superior overall survival with the combination vs dexamethasone alone (median not reached vs 104 weeks; P = .013).
The Len/Dex combination was associated with an increased frequency of several adverse events, primarily neutropenia (grade 1-2, 9% vs 3% with Dex alone; grade 3-4, 27% vs 2%) and thrombocytopenia (grade 1-2, 7% vs 5%; grade 3-4, 10% vs 6%). Pulmonary embolism occurred in 4% of Len/Dex-treated patients and 1% of Dex-treated patients, although no prophylactic anticoagulation was administered. Discontinuation rates were similar between the two treatments (16% with Len/Dex vs 15% with Dex). Thalidomide-associated toxicities, including sedation, constipation, and neuropathy, occurred less frequently with lenalidomide and were of a lower severity.
Dr. Dimopoulos concluded that with the oral Len/Dex regimen, "we now have a patient-friendly combination with robust activity in patients with advanced and refractory multiple myeloma." He predicted that the regimen could provide the basis for transforming multiple myeloma into a more chronic disease.
