The FCR2 Regimen: A Phase 2 Study of FCR-Lite and Lenalidomide in Frontline CLL
FCR remains the standard of care for the treatment of newly diagnosed patients with CLL, but the side-effect profile of the FCR regimen is not trivial, and patients with poor risk features have inferior outcomes on this regimen (Keating MJ, et al. J Clin Oncol. 2005;23:4079-4088; Hallek M, et al. Lancet. 2010;376:1164-1174; Hewamana S, Dearden C. Ther Adv Hematol. 2011;2:147-159). Strategies aimed at minimizing the toxicity of FCR without compromising its efficacy include a dose-reduced approach (Foon KA, et al. Blood. 2012;119:3184-3185; Gozzetti A, et al. Leuk Res. 2014;38:891-895).
At ASH 2014, Mato and colleagues presented the results from a phase 2 study assessing the safety and efficacy of reduced-dose FCR (FCR-lite) plus lenalidomide (FCR2) followed by lenalidomide maintenance therapy in patients with previously untreated CLL (Blood. 2014;124. Abstract 4678). FCR2 consisted of fludarabine 20 mg/m2 on days 1 to 3, cyclophosphamide 150 mg/m2 on days 1 to 3, rituximab 500 mg/m2 on days 1 and 15, and lenalidomide on days 8 to 28 starting at 5 mg and increasing to 10 mg and 15 mg based on toxicity results, every 28 days. Lenalidomide maintenance was initiated after 4 cycles of FCR2 in patients who were minimal residual disease (MRD)-negative in bone marrow and peripheral blood.
Of 19 evaluable patients at a median follow-up of 13.1 months, 47% were in complete remission (CR) after cycle 4 of FCR2, 5% were in CR incomplete, 42% were in partial remission, and 5% had stable disease. After cycle 4, 26% were MRD-negative in bone marrow and 47% were MRD-negative in peripheral blood. These response rates improved after cycle 6 of FCR2, with 63% CR, 50% MRD-negativity in bone marrow, and 75% MRD-negativity in peripheral blood. The most common grade 3/4 AEs included neutropenia, leukopenia, hyperglycemia, and neutropenic fever. In all, 10 patients have gone on to initiate maintenance with lenalidomide.
These data suggest that FCR2 is feasible and demonstrates encouraging clinical activity and an acceptable toxicity profile in a high-risk CLL patient population.