Finite‑Course Venetoclax (BCL‑2) Delivers 36 mo Median PFS in Relapsed Waldenström Macroglobulinemia

Venetoclax, an oral BCL‑2 inhibitor, was given at 200→800 mg daily for up to 2 years in a single‑arm phase 2 trial (NCT02677324) of 32 previously treated WM patients (median follow‑up 81 mo). Median progression‑free survival was 36 mo and treatment‑free survival 43 mo; 72% eventually progressed, yet nine of 17 retreated patients again responded (3 VGPR, 4 PR). Outcomes were unaffected by prior BTK‑inhibitor exposure or CXCR4 status, and no BCL2 G101V resistance mutations emerged. Common toxicities were mild (mainly nausea and diarrhea), with only 9% deaths at 6‑plus years (not due to drug). For context, continuous ibrutinib monotherapy yields a 5‑year PFS of 54% but requires indefinite dosing.