Lenalidomide is safe and active in Waldenström macroglobulinemia

Area of Science:

• Hematology
• Oncology
• Clinical Pharmacology

Background:

• Lenalidomide is effective in multiple myeloma, but its use in Waldenström's Macroglobulinemia (WM) requires dose-finding and safety evaluation.
• Previous combination studies with rituximab suggested potential for significant anemia at high doses in WM.

Purpose of the Study:

• To determine the maximum tolerated dose (MTD) of single-agent lenalidomide in patients with relapsed/refractory WM (RRWM).
• To evaluate the efficacy and safety of lenalidomide in RRWM.

Main Methods:

• A multicenter, dose-escalation, open-label Phase 1/2 study (RV-WM-0426) of oral lenalidomide.
• Lenalidomide was administered at doses escalating from 15 to 20 mg daily on a 21/28-day cycle for 1 year in Phase 1 to establish the MTD.
• Phase 2 was conducted at the MTD, with 17 RRWM patients enrolled.

Main Results:

• The MTD of lenalidomide was determined to be 15 mg/day on a 21/28-day cycle.
• The overall response rate (ORR) was 29% by intention-to-treat (ITT) analysis.
• With a median follow-up of 36 months, the median time to progression (TTP) was 16 months, and the 5-year overall survival (OS) was 91%.
• The most frequent Grade ≥3 adverse events at 15 mg were anemia (14%) and neutropenia (43%).

Conclusions:

• The MTD of lenalidomide in RRWM is 15 mg/day (21/28-day cycle).
• Lenalidomide demonstrates activity and a manageable safety profile in the treatment of RRWM.
• Future research could explore lenalidomide combinations and continuous dosing schedules.