Phase 1 study of lenalidomide, bendamustine, and rituximab in previously untreated patients with chronic lymphocytic leukemia.

Bendamustine-rituximab (BR) is a standard therapy in CLL, and lenalidomide has single-agent activity. This phase 1 study evaluated lenalidomide-BR as initial CLL therapy. Thirteen patients were treated at three dose levels (DL), and an additional 10 were treated at the MTD. The MTD was DL3: lenalidomide 5 mg daily D8-21 of C1, then 10 mg D1-21 of C2-6. One DLT occurred at DL2 (pulmonary embolus). Grade ≥3 toxicities included neutropenia (52.2%), rash (26.1%), anemia (21.7%), thrombocytopenia (21.7%), and febrile neutropenia (13.0%). Of 13, 9 treated at the MTD required dose modification, most for neutropenia (5). OR and CR rates were 87% and 39%, respectively. Lenalidomide-BR could be safely administered and was active as initial CLL therapy, although frequent dose modification at the MTD suggests that lenalidomide 10 mg is too high for most patients. Given the current treatment landscape, lenalidomide combinations warrant evaluation in CLL patients who are chemonaïve but have been failed by the approved targeted therapies.