Evaluation of hypomethylating agents with or without venetoclax in patients with accelerated phase and blast phase myeloproliferative neoplasms: a HERO consortium study.

Patients with accelerated-phase/blast-phase myeloproliferative neoplasms (AP/BP-MPN) experience poor clinical outcomes. A multicenter, retrospective cohort study was conducted to assess outcomes of patients with AP/BP-MPN treated with hypomethylating agent (HMA) regimens. Of 188 patients included, 94 patients received HMA +/- JAK inhibitor and 56 patients received HMA + venetoclax (HMA+ven) +/- JAK inhibitor. The primary endpoint of overall survival (OS) was 9.2 months in both groups (log-rank p = 0.569). The rates of CR/CRi and CR/CRi/MLFS were higher with HMA+ven (36% vs. 11%, p = 0.0002 and 52% vs. 16%, p < 0.0001), but the rate of allogeneic hematopoietic cell transplant (alloHCT) was not different (HMA vs. HMA+ven, 14% vs. 18%, p = 0.51). Multivariate cox regression identified age and receipt of an alloHCT as significant predictors of survival. This large, multicenter, real-world analysis demonstrated the addition of venetoclax to HMA therapy in patients with AP/BP-MPN improved response rates but did not translate into an improvement in OS.