Real-World Outcomes of Hypomethylating Agents and Venetoclax Combination Therapy in AML and Myelodysplastic Syndrome in Pakistan.

Abstract

The combination of venetoclax (VEN) and a hypomethylating agent (HMA) is a standard of care for patients with AML and higher-risk myelodysplastic syndromes (MDS). However, real-world outcomes data from low- and middle-income countries are scarce, where constraints in advanced diagnostics, financial resources, and supportive care infrastructure present unique challenges. This study evaluates the efficacy and safety of this regimen in a resource-limited setting. We conducted a retrospective analysis of 96 patients (AML, n = 54; MDS, n = 42) treated with HMA + VEN at a single center between January 2020 and December 2024. Key outcomes included overall survival (OS), disease-free survival (DFS), and response rates, assessed per standard criteria. The median age was 52 years for patients with AML and 51 years for patients with MDS. In the AML cohort, OS was 77.4% and DFS was 52.8% at 2 years. The overall response rate (ORR) reached 66.6% at end of treatment (EOT), with 55.5% achieving complete remission. In the MDS cohort, 2-year OS was 59.5% and DFS was 44.4%. The most common major toxicity was febrile neutropenia (AML: 66.7%; MDS: 54.8%), although no related mortality occurred. A minority of patients underwent consolidative transplant (AML: 12.9%; MDS: 21.4%). Statistical analysis identified EOT ORR and VEN maintenance as significant for AML OS, while relapse was a critical factor for MDS OS. The HMA-VEN combination is a highly effective and feasible treatment for AML and MDS, even within a resource-limited setting. The findings underscore the critical need for improved supportive care measures, expanded access to molecular diagnostics for risk stratification, and the development of individualized treatment strategies to optimize patient outcomes.