Abstract
Hypomethylating agents (HMA) are indicated in the treatment of higher-risk myelodysplastic syndromes (MDS) and chronic myelomonocytic leukemia (CMML). The combination of hypomethylating agents with venetoclax (Ven) has demonstrated promising results in these diseases, although randomized clinical trials are needed for validation. In this retrospective study, we compared two matched cohorts of patients with MDS or CMML: one receiving oral decitabine-cedazuridine (DEC-C, n = 73) and one receiving DEC-C and Ven (DEC-C-Ven, n = 51), in three contemporary clinical trials. The aim is to determine the impact of the addition of Ven to HMA in MDS and CMML. Individuals were matched using a propensity score approach that was based on the IPSS-M score and age. All patients had excess blasts; 84% were diagnosed with MDS and 16% with CMML. Most patients had high- or very high-risk disease, according to the revised IPSS-R. The overall response rate was superior in the DEC-C-Ven cohort (90% vs 64%, P = 0.002). The median times to best response were 1.1 and 2.7 months for the DEC-C-Ven and DEC-C cohorts, respectively (P < 0.001). More patients underwent hematopoietic stem cell transplantation in the DEC-C-Ven cohort (47%) than in the DEC-C cohort (16%, P < 0.001). The 4- and 8-week mortality did not significantly differ between the DEC-C and DEC-C-Ven cohorts. Patients in the DEC-C-Ven cohort had a more profound neutropenia at days 15 and 21 of the first cycle. The median overall survival was 24 and 19 months for the DEC-C-Ven and DEC-C cohorts, respectively (P = 0.89), and the median event-free survival durations were 18 and 10 months (P = 0.026). In conclusion, the addition of Ven resulted in improved response rates and outcomes in specific subgroups; prospective clinical trials are needed to confirm these findings.