REAL WORLD OUTCOMES OF HYPOMETHYLATING AGENTS AND VENETOCLAX COMBINATION THERAPY IN ACUTE MYELOID LEUKEMIA AND MYELODYSPLASTIC SYNDROME- SINGLE CENTER EXPERIENCE FROM A RESOURCE LIMITED COUNTRY

In this study, we aim to evaluate the safety, efficacy and response rates of venetoclax and HMA combination therapy in patients with AML and MDS. This study provides outcomes from a tertiary care center in Pakistan, giving insights into the outcomes and impact of this therapeutic regimen in a resource-limited country. We conducted a retrospective analysis on 96 patients of which 54 patients had AML and 42 had MDS. All the patients received venetoclax combined with HMA at a single center from January 2020 to December 2024. The primary outcomes measured for AML were Overall Survival (OS), Progression Free Survival (PFS) and response rates (Complete Remission [CR], Partial Remission [PR], Stable Disease [SD] and No Response [NR]) while for MDS response was assessed as per IWG criteria. AML cohort (n = 54) had a male-to-female ratio of 2:1, median age of 52 (IQR:37‒62.2). Risk stratification showed good risk in 3 (5.6%), intermediate in 37 (68.5%) and poor risk in 14 (25.9%) patients. Treatment was given in first line in 41 (75.9%). Indications for first line treatment were age or frailty in 27 (50%), infections in 3 (3.9%) and cardiotoxicity in 2 (3.8%). Total 44 (81.5%) patients received azacytidine and 10 (18.5%) decitabine. Overall Response Rate (ORR) after cycle 1, cycle 2 and EOT was 26 (48.1%), 34 (63%) and 36 (66.7%), CR rate was 15 (27.8%), 27 (50%) and 30 (55.6%) respectively. High dose cytarabine consolidation and venetoclax maintenance were given to 5 (9.3%) and 10 (18.5%) patients respectively. Seven (12.9%) patients underwent HSCT of which 5 (71.4%) received allogenic, 1 haploidentical and 1 received autologous transplant (28.5%). ORR at last follow-up was 27 (50%) of which 24 (88.8%) had CR and 3 (11.1) had CRi. There was no response in 14 (25.9%) and disease relapse in 10 (18.5%) patients. The OS of AML cohort was 77.4% with median 1250 survival days (95% CI 139‒2360) and DFS was 52.8% with median survival 438 days (95% CI 65‒761). The MDS cohort (n = 42) had a male-to-female ratio 9.5:1 with 51-years median age (IQR: 36.5‒57.5). Genetic mutations were present in 3 (7.3%) of which TP53 mutation, del7q were present in 1 each whereas 1 patient had ASXL1, TET2 EZH2, RUNX1 and STAG2 mutations. The median R-IPSS and IPSS scores were 5 (IQR: 4.2‒6) and 1.5 (IQR: 0.75‒2) respectively. Thirty-one (73.8%) patients received azacytidine and 11 (26.2%) decitabine. ORR at cycle 1, cycle 2 and EOT was 12 (28.6%), 21 (51.2%), 18 (42.9%) with CR rates of 2 (4.8%), 11 (26.2%) and 11 (26.2%) respectively. Febrile neutropenia was observed in 23 (54.8%) and cycles were interrupted due to cytopenia’s in 23 (54.8%) patients. Seven (17.1%) patients received allogenic HSCT and 2 (4.9%) received haploidentical HSCT. Five (12.2%) patients received venetoclax maintenance. Eight (21.1%) patients had disease relapse. The OS of MDS cohort was 59.5% with median 907 survival days (95% CI 386‒1424) and The DFS was 44.4% with median survival 528 days (95% CI 336‒719). Venetoclax in combination with HMA represents an effective therapeutic strategy for AML and MDS in the real-world setting, even in resource limited settings.