Lenalidomide is safe and active in Waldenström macroglobulinemia

Abstract

Purpose. Lenalidomide is manageable and effective in Multiple Myeloma, particularly in elderly patients. Surprisingly, the combination of lenalidomide with rituximab produced clinically significant anemia at 25mg/day for 21/28 days, the highest possible dose, in Waldenström's Macroglobulinemia (WM). We aimed to determine the maximum tolerated dose (MTD) of single agent lenalidomide and determine its impact on WM. Materials and methods. RV‐WM‐0426 is a multicenter dose escalation open label phase 1/2 study of lenalidomide in relapsed/refractory WM (RRWM). Lenalidomide was given orally 21/28 days per cycle for one year, at escalated dose of 15 to 20 mg during phase 1 to determine the MTD; the phase 2 part was conducted at the MTD. Results. 17 RRWM patients were included. The MTD was established at 15 mg/day 21/28. By ITT analysis, the overall response rate was 29%. With a median follow‐up of 36 months, median TTP was 16 months (95%CI 5.5‐26), the 5‐year OS was 91%. The most frequent AE ≥ grade 3 at 15mg were 14% anemia and 43% neutropenia. Conclusion. The MTD of lenalidomide is 15mg/day 21/28 days in RRWM. Lenalidomide is active in the treatment of RRWM and the safety profile appears manageable. Future studies may look into combinations of lenalidomide and continuous dosing.