Long-term follow-up of venetoclax monotherapy in previously treated patients with Waldenström macroglobulinemia Open Access

• Venetoclax provides durable responses in previously treated WM with a median PFS of 36 months. Superior PFS was seen when attaining ≥PR.

• BCL2 G101V mutations were not detected in patients who completed venetoclax therapy. Re-treatment with venetoclax induced deep responses.

Venetoclax is highly active in previously treated Waldenström macroglobulinemia (WM). However, data on long-term durability and retreatment with venetoclax remain limited. Herein, we present an update of a prospective clinical trial of finite-duration venetoclax on 32 previously treated patients with WM. With a median follow-up of 81 months, twenty-three patients (72%) had disease progression, 17 (53%) began a new treatment, and 3 (9%) had died. The median progression-free survival (PFS) was 36 months, and the median treatment-free survival (TFS) was 43 months. PFS and TFS were superior in patients who attained at least a partial response to therapy. CXCR4 mutations or previous BTK inhibitor exposure did not impact these outcomes. Of the 17 patients who started a new therapy after completion of venetoclax therapy, nine were retreated with venetoclax alone or in combination (three attained a very good partial response, four a partial response, one had stable disease, and one did not respond). No BCL2 G101V mutations were detected in 52 CD19-selected bone marrow samples from 27 patients during treatment. Venetoclax induces durable responses in WM, allowing for retreatment in patients who progressed after completing therapy without the emergence of BCL2 G101V mutations. Clinical Trial Information: NCT02677324