Clinical Efficacy of Lenalidomide {Revlimid®} in Patients with Relapsed or Refractory Chronic Lymphocytic Leukemia (CLL): Updated Results of a Phase II Clinical Trial.

Introduction: Lenalidomide (L) is an immunomodulatory agent (IMiD®), recently approved for treatment of patients (pts) with previously treated multiple myeloma and del 5q- MDS. Its antitumor effects are reported to be mediated at least in part through modulation of both the cytokine and the immune cellular tumor microenvironment. Clinical efficacy of L in pts with B-CLL has not been investigated previously. In a phase II clinical study, we examined the antileukemic effects of L in pts with relapse (rel) or refractory (ref) B-CLL. Patients and Methods: CLL pts with rel or ref disease were eligible. L was given at 25mg PO QD from days 1–21 of 28-day cycle. Response was assessed every month using the NCI-WG 1996 criteria. Treatment with L was continued until progressive disease (PD) or molecular complete response (CR). Pts with PD received rituximab (R) (375mg/m2) with L. Target enrollment was 45 patients. Results: Forty-five pts, median age of 64 years (range: 42–75) were enrolled. Advance stage disease was noted in 64%, elevated B2M in 24% and fludarabine refractory disease in 51% of the pts. Pts had a median of 3 prior therapies (range 1–10). All pts are evaluable for toxicity. Thrombocytopenia and neutropenia were the most common hematologic toxicity while fatigue and flare reaction (sudden, tender enlargement of lymph node, liver and/or spleen, with or without rash, low grade fever and/or increase in white blood counts) were the most common non-hematologic complications. Two patients experience reversible tumor lysis syndrome. On an intent-to-treat analysis, overall response rate was 42% with complete remission in 9% (n=4) and partial remission in 33% (n=15) of the pts. Molecular complete response (determined by PCR) was noted in 3 pts. Twelve pts were inevaluable (unable to complete 2 treatment cycles; either for toxicity or consent withdrawal) 4 are too early for response evaluation. Response rate among evaluable patients was 65.5% (19/29). To date only 2 pts have required the addition of R to L due to PD. Both have achieved a PR with combination therapy. Correlative studies: we evaluated baseline T and NK cell repertoire, modulation of cytokines (VEGF, IL-10, IL-6, TNF-alpha) as well as modulation of gene expression profiles before and after treatment with L, this data will be presented at the meeting. Conclusion: L is clinically active in pts with rel/ref CLL. CR’s, as well as, molecular CR determined by PCR were achieved with single agent L. Interestingly, in pts who developed resistance to L alone, addition of R resulted in a clinical response. These results are exciting and warrant further investigation of L in CLL pts. Final results of this study will be presented at the meeting.