A randomized phase 2 study of lenalidomide therapy for patients with relapsed or relapsed and refractory multiple myeloma

Abstract

This multicenter, open-label, randomized phase 2 study evaluated 2 dose regimens of lenalidomide for relapsed, refractory myeloma. Seventy patients were randomized to receive either 30 mg once-daily or 15 mg twice-daily oral lenalidomide for 21 days of every 28-day cycle. Patients with progressive or stable disease after 2 cycles received dexamethasone. Analysis of the first 70 patients showed increased grade 3/4 myelo-suppression in patients receiving 15 mg twice daily (41% versus 13%, P = .03). An additional 32 patients received 30 mg once daily. Responses were evaluated according to European Group for Blood and Marrow Transplantation (EBMT) criteria. Overall response rate (complete, partial, or minor) to lenalidomide alone was 25% (24% for once-daily and 29% for twice-daily lenalidomide). Median overall survival in 30-mg once-daily and twice-daily groups was 28 and 27 months, respectively. Median progression-free survival was 7.7 months on once-daily versus 3.9 months on twice-daily lenalidomide (P = .2). Dexamethasone was added in 68 patients and 29% responded. Time to first occurrence of clinically significant grade 3/4 myelosuppression was shorter in the twice-daily group (1.8 vs 5.5 months, P = .05). Significant peripheral neuropathy and deep vein thrombosis each occurred in only 3%. Lenalidomide is active and well tolerated in relapsed, refractory myeloma, with the 30-mg once-daily regimen providing the basis for future studies as monotherapy and with dexamethasone.

Figure 1.

Overall survival and progression-free survival of lenalidomide-treated patients. (A) Overall survival for the 15-mg twice-daily and 30-mg once-daily dose groups. (B) Overall survival combined for both doses with 95% confidence interval. (C) Progression-free survival to lenalidomide (without censoring for addition of dexamethasone) for the 15-mg twice-daily and 30-mg once-daily dose groups. (D) Progression-free survival to lenalidomide (without censoring for addition of dexamethasone) for both doses combined (with 95% confidence interval). (E) Overall progression-free survival (with censoring for addition of dexamethasone) for 15 mg twice-daily and 30 mg once-daily dose groups. (F) Overall progression-free survival (with censoring for addition of dexamethasone) for both doses combined with 95% confidence interval. Dotted lines in panels B, D, and F represent the upper and lower boundaries of the 95% CI for each Kaplan-Meier curve.

Figure 2.

Change in serum sICAM-1 levels during single-agent lenalidomide treatment. Baseline (beginning of first cycle) versus beginning of second cycle.

Figure 3.

Pharmacokinetics of lenalidomide treatment. (A) Minimum lenalidomide plasma levels for the 30-mg once-daily dose group. (B) Minimum lenalidomide plasma levels in the 15-mg twice-daily dose group. Lenalidomide (CC-5013): mean ± SE.