HMA ± venetoclax combinations in accelerated- and blast-phase MPN

Results from a multicenter, retrospective HERO Consortium cohort study evaluating hypomethylating agent (HMA) combinations in 188 patients with accelerated phase/blast phase (AP/BP) myeloproliferative neoplasms (MPN) were published in Leukemia & Lymphoma by Ciervo et al. Patients received HMA ± Janus kinase inhibitor (JAKi; n = 94) or HMA + venetoclax ± JAKi (n = 56). The primary endpoint was overall survival (OS).

Key data: At a median follow-up of 8.6 months, median OS was 9.2 months in both groups 
(log-rank p = 0.569). Rates of allogeneic hematopoietic stem cell transplant (allo-HSCT) were similar among patients who received HMA + venetoclax and those who received HMA alone (18% vs. 14%; p = 0.51). Median OS in patients who underwent allo-HSCT was 22.0 months vs 9.2 months in those who did not (p < 0.001). Complete response/complete response with incomplete count recovery (CR/CRi) rates were significantly higher in the HMA + venetoclax group vs the HMA group (36% vs 11%; p = 0.0002), as were CR/CRi plus morphologic leukemia-free state (MLFS) rates (52% vs. 16%; p < 0.0001). In multivariable analysis, age (hazard ratio [HR], 1.04; 95% confidence interval [CI], 1.01–1.06; p = 0.011) and receipt of allo-HSCT (HR, 0.40; 95% CI, 0.20–0.79; p = 0.008) were significant predictors of OS. In the HMA + venetoclax group vs HMA group, febrile neutropenia occurred in 58% vs 54% of patients and infections occurred in 42% vs 45% of patients.

Key learning: In this real-world cohort study, the addition of venetoclax to HMA therapy improved response rates but did not translate to improved OS in patients with AP/BP-MPN, highlighting the continued unmet need for effective therapies in this population.