Revlimid is an orally administered derivative of thalidomide, which is a very active agent for the treatment of multiple myeloma but has serious side effects, especially thromboembolism. Revlimid is reported to have less toxicity than thalidomide but retains antimyeloma effects. Revlimid has recently been approved by the FDA for review of treatment of myelodysplastic syndromes (MDS) wih a 5q- mutation and for first line treatmetn of multiple myeloma in conjunction with dexamethasone. Revlimid is in clinical trials for the evaluation of treatment for other hematologic cancers including CLL.
Researchers from the Roswell Park Cancer Center and the Toronto Sunnybrook Regional Cancer Center have reported that Revlimid has significant activity in CLL. This study was also presented at the 2005 meeting of the American Society of Hematology in December 2005. Thalidomide has also demonstrated activity when combined with Fludara for initial treatment of CLL.This was a small study involving only 16 patients, but the complete response rate was over 50%.
The study presented at ASH 2005 and ASCO 2006 involved 29 patients with relapsed or refractory CLL. More than 50% has failed Rituxan combinations and more than 50% had failed fludarabine combinations. The complete response rate was 15%, the partial response rate was 53% and an additional 15% had stable disease. Two patients had complete molecular responses. The most common side effects reported were fatigue, neutropenia and thrombocytopenia. Approximately 60% had “flare reaction”—described as tender swelling of lymph nodes and rash—which was successfully treated with steroids. In-vitro studies showed an increased number of natural killer cells but no increase in apoptosis.
Many studies are now underway to evaluate the activity of Revlimid in combination with rituximab in patients with lymphoma. The initial analysis of the first 46 patients of a 200 patient phase-II, multi-center open-label clinical study, NHL-003, shows encouraging results that are consistent with those of the earlier NHL-002 trial (Abstract #2565). Responses were seen across all sub-types of NHL. Furthermore, prognostic factors have been identified that may be predictive of response to REVLIMID monotherapy. The study reported that overall response to single agent lenalidomide was 28%, with 6 responses in the diffuse large B-cell lymphoma group (21%) and 5 in the mantle cell lymphoma group (38%). Ten patients had stable disease (SD). This was reported at ASH in December 2007.
Although some question tolerability of the 25mg dose, there are now several supportive phase II studies and I considered the literature to support this treatment.
Habermann TM, Lossos IS, Justice G, et al. Lenalidomide oral monotherapy produces a high response rate in patients with relapsed or refractory mantle cell lymphoma. British Journal of Haematology. 2009;145:344-349.
Vose JM, Zinzini PL, Reeder CB, et al. Confirmation of the efficacy and safety of lenalidomide oral monotherapy in patients with relapsed or refractory diffuse large-B-cell lymphoma: Results of an international study *NHL-003). Blood. 2008;112:103, abstract 268.
M. S. Czuczman, C. B. Reeder, J. Polikoff, N. M. Chowhan, I. Esseessee, R. Greenberg, A. Ervin-Haynes, D. Pietronigro, J. B. Zeldis, T. E. Witzig International study of lenalidomide in relapsed/refractory aggressive non-Hodgkin's lymphoma. J Clin Oncol 26: 2008 (May 20 suppl; abstr 8509)