Mantle cell lymphoma (MCL) is considered an aggressive and incurable B-cell
malignancy despite current available treatments that include the incorporation of
rituximab,
bortezomib, high-dose
cytarabine, and for those eligible, high dose
chemotherapy and autologous bone marrow transplant (HDC-ASCT). Patients with relapsed/refractory MCL represent a challenge for the treating physician stressing the need to develop therapeutic agents.
Lenalidomide, a novel inmmunomodulatory
drug (IMiD), is a promising therapeutic strategy for patients with relapsed/refractory
B-cell lymphoma. Biologically, the mechanisms responsible for
lenalidomide activity are yet to be clearly defined. Based on pre-clinical models and early correlative studies conducted parallel to clinical trials,
lenalidomide has been found to enhance NK-cell and T-cell activity against
tumor cells, alter the balance of pro- and anti-inflammatory
cytokines in the
tumor bed, inhibit angiogenesis, and to a lesser degree, induce cell cycle arrest and apoptosis in
cancer cells. Together, all these
biological effects appear to play a role in the activity observed in
lymphoma patients treated with
lenalidomide. Given the effect in NK- and T-cell function,
lenalidomide is an alternative strategy to enhance the anti-
tumor activity of
monoclonal antibodies (mAbs). Clinical responses have been observed in patients with relapsed/refractory
chronic lymphocytic leukemia (CLL),
follicular lymphoma,
small lymphocytic lymphoma,
diffuse large B-cell lymphoma (DLBCL), and MCL. The favorable toxicity profile and route of administration made the use of
lenalidomide an attractive
therapy for certain types of patients (i.e. elderly,
chemotherapy unfit, etc.). The erratic but serious incidence of
tumor lysis syndrome and/or
tumor flare reactions provides challenges in the incorporation of
lenalidomide in the management of previously untreated
lymphoma patients with bulky
adenopathy. Early studies evaluating the efficacy and toxicity of
lenalidomide in combination with
steroids or
rituximab/
bendamustine in MCL are promising and warrant further study. In addition, the evaluation of
lenalidomide in the maintenance setting (i.e. post HDC-ASCT) or in combination with other target specific agents (i.e.
proteasome inhibitors) in MCL is being addressed in ongoing clinical trials. We provide a general overview of the clinical development of
lenalidomide in MCL. Future translational and clinical studies will further define the role of
lenalidomide in the management of de novo or relapsed/refractory MCL and may assist in the identification of subset of MCL patients most likely to gain clinical benefit from this exiting agent.