Venetoclax in combination with hypomethylating agents in chronic myelomonocytic leukemia: a propensity score matched multicenter cohort study

Chronic myelomonocytic leukemia (CMML) is a rare hematologic malignancy with overlapping features of myelodysplastic neoplasm (MDS) and myeloproliferative neoplasms characterized by peripheral blood monocytosis [1]. There is a predisposition for transformation to acute myeloid leukemia (AML), termed CMML with blast transformation (CMML-BT) [2, 3]. Hypomethylating agents (HMAs) are the sole FDA approved therapy for CMML albeit without established efficacy in terms of prolonging overall survival (OS) and halting disease evolution [4,5,6]. In order to improve response rates, venetoclax (VEN) has been combined with HMAs extrapolating data from AML and MDS [7, 8]. Single centers have offered varied results on the added benefit of VEN to HMA therapy in CMML and CMML-BT [9,10,11], but these studies lack control cohorts and are limited by small sample sizes of patients evaluated in each treatment setting and disease category.

To clarify the role of upfront HMA + VEN in patients with CMML and CMML-BT, we performed a multicenter retrospective cohort study utilizing a propensity score matched (PSM) cohort of patients treated with HMA alone.