ATLANTA—The combination of lenalidomide (Revlimid) with melphalan(Drug information on melphalan) and prednisone(Drug information on prednisone) (R-MP) is highly active and well tolerated in older adults with newly diagnosed multiple myeloma, finds a phase I/II trial. Antonio Palumbo, MD, of the University of Torino in Italy, presented results of the trial at the 42nd Annual Meeting of the American Society of Clinical Oncology (abstract 7518).

The trial enrolled 53 patients age 65 or older with newly diagnosed, symptomatic multiple myeloma, divided into four cohorts. Cohorts 1 and 2 received a lower and higher dose of melphalan, respectively, with prednisone (4 days every 4 to 6 weeks) plus lenalidomide 5 mg/d (21 days every 4 to 6 weeks). Cohorts 3 and 4 received the lower and higher dose of melphalan, respectively, with prednisone plus a higher lenalidomide dose (10 mg/d). Patients received up to nine cycles.

The overall rate of response (complete, very good partial, partial, and minor) in the 41 evaluable patients after one cycle with R-MP was 93%. This exceeded the 64% response rate after six cycles with MP seen in historical controls—65 patients treated with MP alone or with thalidomide(Drug information on thalidomide) (MPT) (Lancet 367:825-831, 2006). Dr. Palumbo pointed out that 65% of patients had a partial or very good partial response with R-MP in the first cycle. "This is something we have to keep in mind because the tumor reduction is so fast that the toxic adverse events will be mainly concentrated in the first one or two courses of therapy," he said.

The overall response rate after a median of seven cycles of R-MP (100%) exceeded that of the historical controls given MPT (81%). "We still have to go to nine cycles," Dr. Palumbo noted. "And we have seen that while partial response is very fast, within the first two cycles, the complete responses are coming along throughout the treatment. So possibly there will be more complete responses with cycles 8 and 9."

Patients in cohorts 3 and 4 had identical overall response rates (100%), but those in cohort 3 (lower melphalan dose) had higher rates of complete and very good partial responses. "The impression is that we had a higher response rate in cohort 3 because we were able to recycle exactly at the same day, while with the higher dose of melphalan, we had a high proportion—one out of four patients—who had a delay in their cycle, and therefore we lost the dose intensity of lenalidomide," Dr. Palumbo commented. "But this is also telling us something else—that we need continuous treatment with this drug. When we stop treatment with lenalidomide, we reduce the efficacy of the combination."

Preliminary data show an estimated rate of event-free survival of 87% at 16 months with R-MP (median follow-up, 9.6 months), compared with 71% at 18 months in the historic controls given MPT (median follow-up, 17.6 months).

Toxicities

There were no dose-limiting toxicities during the first cycle of therapy in cohorts 1 and 2, but several in cohorts 3 and 4 (higher lenalidomide dose), which became the main focus of the trial, Dr. Palumbo said. Among the 41 patients in cohorts 3 and 4, toxicities occurred primarily in the first two cycles of therapy, he noted. Grade 3-4 hematologic toxicities in these patients were neutropenia (approximately 65%), thrombocytopenia (35%), and anemia (15%), but two-thirds of these events occurred in cohort 4 (higher melphalan dose).