Revlimid for refractory relapsed B-cell lymphoma – pro

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 treatment of multiple myeloma in conjunction with dexamethasone. Revlimid is in clinical trials for the evaluation of treatment for other hematologic cancers.

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 adn others are ongoing.

A 2009 paper by Witzig concluded: “Oral lenalidomide monotherapy produces durable responses with manageable adverse events in patients with relapsed/refractory indolent NHL, warranting further investigation of treatment for indolent NHL.”

Newer studies confirm that lenalidomide is effective for relapsed or refractory large B-cell lymphomas as well.Llenalidomide represented an active drug on aggressive relapsed NHL. There are positive trials in this setting of Revlmid used without rituximab and ones that added rituximab.  Monotherapy as well as use with rituximab with lenalidomide showed an activity in term of overall response rate, with acceptable hematological and extrahematological toxicities in relapsed/refractory aggressive NHL.

T. E. Witzig et al, A comprehensive review of lenalidomide therapy for B-cell non-Hodgkin lymphoma.  Ann Oncol (2015) doi: 10.1093/annonc/mdv102

Annalisa Chiappella and Umberto Vitolo. Review Article Lenalidomide in Diffuse Large B-Cell Lymphomas
dvances in Hematology. Volume 2012 (2012), Article ID 498342, 5 pages

Thomas E. Witzig et al,
Lenalidomide Oral Monotherapy Produces Durable Responses in Relapsed or Refractory Indolent Non-Hodgkin’s Lymphoma, JCO November 10, 2009 vol. 27 no. 32 5404-5409

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)

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