Abstract
Venetoclax showed promising activity in a small phase II trial in relapsed/refractory Waldenström macroglobulinemia (WM). To report the clinical activity of venetoclax and prognostic factors associated with outcomes in a larger cohort, we retrospectively identified 76 patients with relapsed/refractory lymphoplasmacytic lymphoma (LPL)/WM treated with venetoclax monotherapy at nine US medical centers. The median age at venetoclax treatment initiation was 66 years. MYD88, CXCR4, and TP53 mutations were detected in 65 (94%), 23 (40%), and 10 (22%) patients, respectively. The median number of prior lines of treatment was 3, including covalent BTK inhibitor in 82% and alkylating agent in 71% of patients. The overall and major response rates to venetoclax were 70% and 63%, respectively. The median and 2-year progression-free survival (PFS) were 28.5 months and 57%, respectively. The median and 2-year overall survival were not reached and 82%, respectively. Prior treatment with BTK inhibitor was the only factor associated with PFS in multivariate analysis (hazard ratio 2.97, p = 0.012). Venetoclax dose interruptions and/or reductions occurred in 27 patients (41%). Five patients (7%) developed laboratory tumor lysis syndrome (TLS), including 3 (4%) with clinical TLS. Venetoclax resulted in a high response rate and a prolonged PFS in patients with heavily pretreated LPL/WM.