Real world outcomes of venetoclax combined with hypomethylating agents in acute myeloid leukemia and myelodysplastic syndrome: Insights from a tertiary care centre in Pakistan.

e18532 Background: Acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) are hematologic malignancies associated with dismal outcomes in elderly and frail patients. venetoclax(ven),in combination with hypomethylating agents (HMA) has shown clinical efficacy in treatment of these disorders. Data from resource limited settings is however scarce. Methods: We conducted a retrospective analysis of patients with AML and MDS who received ven combined with HMA at a single center from January ,2020 to December 2024.The primary outcomes were overall survival(OS),progression free survival(PFS) and response rates as per ELN 2022 while for MDS as per IWG criteria. Results: Total 96 patient received treatment, including 54 (55.6%) patients of AML and 42 (43.3%) of MDS. Among AML patients, male-to-female ratio was 2:1 and median age 52 years (IQR:37- 62.2). Three (5.6%) patients had good risk disease as per ELN while intermediate risk was in 37(68.5%) and poor risk in 14 (25.9%). First line treatment was given in 41 (76%) patients. Indications were relapsed disease in 6 (11.1%) and primary refractory in 5 (9.3%). Indications for first line treatment were advanced age or frailty in 27 (50%) , active infections in 3 (3.9%) and cardiac dysfunction in 2 (3.8%) .Total 44 (81.5%) patients received azacytidine and 10 (18.5%) decitabine. Median number of cycles given were 3 (IQR: 2-6). Response rate (ORR)after cycle 1 was 26 (48.1%) including 15 (27.8%) CR , 5 (9.3%) CRi and 6 (11.1%) PR. ORR after cycle 2 was 34 (63%) including 27 (50%) CR , 3 (5.6%) CRi and 4 (7.4%) PR. Response rate (ORR) at end of treatment was 36 (66.7%) including 30 (55.6%) in CR , 4 (7.4%) in CRi and 2 (3.7%) PR. The OS was 77.4% with median 1250 survival days (95% CI:139-2360). The DFS was 52.8 % with median survival 438 days (95% CI:165-761) . For MDS patients, male-to- female ratio was 9.5:1 with 51 years median age (IQR:36.5- 57.5).The median R-IPSS and IPSS score 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 was 12 (28.6%) including 2 (4.8%) CR. ORR at cycle 2 was 21 (50%) including 11 (26.2%) CR. ORR at end of treatment was 18 (42.9%) including 11 (26.2%) CR. The OS was 59.5% with median 907 survival days (95% CI: 386-1424) and DFS was 44.4 % with median survival 528 days (95% CI: 336-719). Conclusions: Venetoclax with HMAs represent an effective therapeutic strategy for AML and MDS in the real-world setting. This regimen is associated with promising outcomes and may offer an alternative to traditional treatment regimens for patients in Pakistan and similar settings.