Reduced‐dose fludarabine, cyclophosphamide, and rituximab (FCR‐Lite) plus lenalidomide, followed by lenalidomide consolidation/maintenance, in previously untreated chronic lymphocytic leukemia

Abstract

Fludarabine, cyclophosphamide and rituximab (FCR) remains the standard of care for fit chronic lymphocytic leukemia (CLL) patients requiring first therapy. However, side effects can be significant, and patients with poor risk features have inferior outcomes. The purpose of this study was to evaluate reduced‐dose FCR (FCR‐Lite) plus lenalidomide (FCR²) followed by lenalidomide maintenance as a strategy to shorten immunochemotherapy in untreated CLL. Patients received 4–6 cycles of FCR². Patients who were minimal residual disease (MRD) negative in peripheral blood (PB) and bone marrow (BM) initiated 12 months of lenalidomide maintenance after either 4 or 6 cycles (based on MRD status). The primary study endpoint was the complete response (CR) rate after 4 cycles of FCR². Twenty patients were evaluable. After 4 cycles of FCR², response rates were: CR, 45.0%; CR with incomplete blood count recovery (CRi), 5.0%; partial response (PR), 45.0%; stable disease (SD), 5.0%. BM and PB samples from 27.8% and 52.9% of patients, respectively, were MRD negative. After 6 cycles, response rates were: CR, 58.3%; CRi, 16.7%; PR, 25.0%. BM and PB samples from 50.0% and 72.7% of patients, respectively, were MRD negative. Overall, 75% of evaluable patients achieved a CR or CRi following FCR². After 17.4 months' median follow‐up, one progression and one death have occurred. Our findings suggest that FCR² combines encouraging clinical activity with acceptable toxicity in previously untreated CLL. Lenalidomide can be safely added to FCR, and may reduce chemotherapy exposure without compromising outcomes.