, Volume 28, Issue 8 Supplement, pp 1-13
Date: 29 Nov 2011

Continued treatment with lenalidomide in multiple myeloma

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Abstract

Lenalidomide is a more potent and better tolerated immunomodulatory drug (IMiD) as compared to thalidomide, the first-in-class IMiD. The mechanism of action of lenalidomide in multiple myeloma (MM) includes direct antitumor, immunomodulatory, and regulatory effects on the plasma cell-bone marrow niche interaction. Lenalidomide in combination with dexamethasone has shown a significantly higher efficacy as compared to dexamethasone alone in the treatment of relapsed or refractory MM in terms of overall response (OR) rate, complete response (CR) rate, time to progression (TTP), and overall survival (OS). Dosing, duration, and overall benefit of dexamethasone combination remains to be elucidated in ad-hoc trials, which may impact the tolerability and efficacy of the recommended schedule of lenalidomide rescue treatment. Depth of response achieved with lenalidomide and dexamethasone is associated with improvements in response duration, TTP, and OS, regardless of when the response is achieved. Although the probability of achieving a CR or very good partial response (VGPR) decreases over time, patients who are able to tolerate treatment in the absence of disease progression continue to experience benefits. However, optimal duration of rescue treatment from the time-point of best response has not been formally established. Recent data from phase 3 clinical trials also suggest the benefit of single-agent lenalidomide as maintenance after first-line treatment, and of lenalidomide combination therapy with conventional chemotherapy or new agents as induction treatment, in both autologous stem cell transplantation (ASCT) eligible and ineligible MM patients. Concerns about second primary neoplasms have been recently raised, and need further investigation. Taken together, these facts open new clinical settings in which lenalidomide therapy may benefit MM patients and deepen IMiD knowledge, especially in the continued rescue treatment and maintenance settings. Further study is warranted to optimize treatment with IMiDs.