HMA + venetoclax as frontline therapy in MPN-BP: A real-world study

Results from a retrospective, multicenter, real-world study evaluating hypomethylating agents (HMA) + venetoclax as frontline therapy in 61 patients with blast-phase myeloproliferative neoplasms (MPN-BP) were recently published in Leukemia Research by Latagliata et al. Measures of treatment response included the composite overall response rate (ORR), defined as the sum of acute leukemia response-complete (ALR-C)/ALR-C with incomplete hematologic recovery (ALR-Ci) plus acute leukemia response-partial (ALR-P).

Key data: The ORR with HMA + venetoclax was 60.6% (ALR-C/Ci, 42.6%; ALR-P, 18.0%), with a median response duration of 9.4 months (95% confidence interval [CI], 4.3–18.3). Median overall survival (OS) was 10.5 months (95% CI, 7.7–13.3). Patients with any type of response to HMA + venetoclax (ALR-C/Ci + ALR-P) had a longer OS (13.6 months; 95% CI, 10.3–21.9) vs those with progressive/stable disease (7.1 months; 95% CI, 4.4–11.7; p < 0.001). Grade 3/4 hematologic toxicity occurred in 83.6% of patients, including severe neutropenia in 81.9%. Thrombocytopenia occurred in 52.4% of patients, and 90.1% required red blood cell transfusions; 52.4% of patients had at least one infective episode.

Key learning: In this real-world study, HMA + venetoclax demonstrated encouraging response rates in patients with MPN-BP, with an ORR exceeding 50%. However, the short response duration, a median OS of <12 months, and high rates of adverse events (AEs), highlight the need for improved therapeutic approaches in this patient population.