Prolonged Overall Survival with Lenalidomide Plus Dexamethasone Compared with Dexamethasone Alone in Patients with Relapsed or Refractory Multiple Myeloma.

Abstract Introduction: Lenalidomide (Len), an analog of thalidomide (Thal) is a novel, oral, immunomodulatory agent that is effective against multiple myeloma (MM). In 2 prospective, randomized, double-blind, placebo-controlled phase III trials, Len with dexamethasone (Dex) induced a significantly higher overall response (OR) rate and complete remission (CR) rate, as well as longer time-to-progression (TTP) in comparison with Dex alone. Here, we investigate the long-term overall survival (OS) with Len/Dex. Methods: We evaluated the pooled results from both randomized trials (MM-009, MM-010) of 704 patients who had relapsed or refractory MM, without prior resistance to Dex, who received either Len (25 mg daily for 3 weeks every 4 weeks), or placebo. Dex was given at 40 mg on days 1–4, 9–12, 17–20 every 4 weeks for 4 cycles. From cycle 5 onwards, Dex was given at 40 mg on days 1–4 only. Response rate and TTP are based on data obtained before unblinding (June 2005 [MM-009] and August 2005 [MM-010]). Follow-up data on OS were obtained up to January 2007. Forty-seven percent of patients who received placebo/Dex crossed over to receive Len +/− Dex. Results: Of 704 patients, 353 were treated with Len/Dex and 351 with Dex alone. Baseline characteristics were well balanced between patients receiving Len/Dex and those receiving Dex alone. Median TTP, OR, and CR were significantly improved in patients treated with Len/Dex compared with Dex alone (Table). Of patients who progressed on Dex alone prior to unblinding, or were found to be receiving Dex alone after unblinding, 47% crossed over to Len +/− Dex. Despite these patients crossing over to Len +/− Dex at progression or at the time of unblinding, the OS was significantly improved in patients treated with Len/Dex compared with Dex alone (hazard ratio 1.295; 95% confidence interval 1.040–1.614; p=0.02). Median OS in the Len/Dex group was 35 months and 31 in the Dex alone group (p<0.05). Median OS was also significantly longer with Len/Dex compared with Dex alone in patients with more than 1 prior therapy (32.4 months versus 27.3 months, p<0.05). Similar median OS was observed with Len/Dex and Dex alone in patients with 1 prior therapy (median OS not yet reached and 35.3 months, p=0.24). Conclusion: With increased follow-up and despite cross-over, patients treated first with Len/Dex had significantly improved OS compared with those treated with Dex alone. Len/Dex (n=353) Dex alone (n=351) P value OR, % 60.6 21.9 <0.001 CR, % 15.0 2.0 <0.001 Median TTP, months 11.2 4.7 <0.001 Median OS, months 35.0 31.0 <0.05 Median OS in patients with 1 prior treatment, months not yet reached 35.3 0.24 Median OS in patients with >1 prior treatment, months 32.4 27.3 <0.05