Lenalidomide plus Dexamethasone Has Similar Tolerability and Efficacy in Treatment of Relapsed/Refractory Multiple Myeloma Patients with or without History of Neuropathy.

Neuropathy in multiple myeloma, related either to the disease itself or as a result of anti-myeloma treatment, may limit patients' therapeutic options.

To assess efficacy and safety of lenalidomide + dexamethasone treatment in relapsed/refractory multiple myeloma patients depending on reported neuropathy history.

This subanalysis is based on pooled data from two large multi-center randomized placebo-controlled phase-3 trials (MM-009, MM-010), for patients who had received at least one prior therapy of multiple myeloma. Patients were randomized to receive either 25 mg of lenalidomide or placebo on Days 1-21 of a 28-day cycle. Both groups also received 40mg of oral dexamethasone on Days 1-4, 9-12, and 17-20 for the first four cycles, after which dexamethasone was administered only on Days 1-4. All patients who received lenalidomide + dexamethasone during the study period were included in this subanalysis (n=353). Patients with a reported history of neuropathy between time of first multiple myeloma diagnosis and date of study randomization (n=70) were compared to patients without a reported history of neuropathy (n=283). Adverse event terms included were: non-specified neuropathy, peripheral motor neuropathy, non-specified peripheral neuropathy, peripheral sensory neuropathy and non-specified polyneuropathy. Lenalidomide mean and median daily dose intensity, duration of treatment and efficacy [including complete response (CR), very good partial response (VGPR), time to progression (TTP) and overall survival (OS)] were assessed.

Lenalidomide mean daily dose intensity (excluding treatment breaks on Days 22-28 of each 28-day cycle) was not significantly different between patients with or without history of neuropathy (21.6 mg vs. 22.6 mg; p=0.1479). In addition, the median daily dose intensity was equivalent to the planned daily dose of 25mg (p=0.3857). Mean and median treatment duration were also not significantly different between the two groups (10.1 vs. 10.7 months, p = 0.5307, respectively 9.6 vs. 10.2 months, p=0.5473). Response rates were not significantly different for patients with or without history of neuropathy, with CR/VGPR of 40% vs. 33% (p=0.3116) and overall response rates of 68% vs. 64% (p=0.6174), respectively. Time to progression was not significantly different between the two groups (median TTP 14.8 vs. 12.3 months, p=0.6488), and neither was overall survival (median OS not yet reached vs. 30.6 months, p=0.7848).

With median daily dose intensities both at 25mg and a comparable mean daily dose intensity at 21.6 and 22.6 mg, lenalidomide is well tolerated in both patients with and without history of neuropathy. With a favorable tolerability profile, patients are able to continue therapy for longer, achieving desired response, longer TTP, and ultimately longer overall survival. The results of these data demonstrated that lenalidomide + dexamethasone is an optimal therapeutic choice in relapsed or refractory multiple myeloma irrespective of a patient's history of neuropathy.

Delforge:Celgene: Honoraria, Speakers Bureau; Janssen-Cilag: Consultancy, Honoraria. Facon:Janssen Cilag: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Bravo:Celgene: Employment. Dimopoulos:Celgene: Honoraria.