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

abstractVenetoclax is highly active in previously treated Waldenström macroglobulinemia (WM). However, data on the 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, 23 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 Bruton tyrosine kinase inhibitor exposure did not impact these outcomes. Of the 17 patients who started a new therapy after completion of venetoclax therapy, 9 were retreated with venetoclax alone or in combination with other treatments (3 attained a very good partial response, 4 attained a partial response, 1 had stable disease, and 1 did not respond). No BCL2 G101V mutations were detected in 52 CD19-selected bone marrow samples from 27 patients during treatment. Venetoclax induced durable responses in WM, thereby enabling retreatment in patients who progressed after completing therapy without the emergence of BCL2 G101V mutations. This trial was registered at www.ClinicalTrials.gov as #NCT02677324.