: The combination of cladribine (CLAD), low-dose cytarabine (LDAC), and venetoclax (CLAD-LDAC-venetoclax) has demonstrated promising efficacy in acute myeloid leukemia (AML) but remains underutilized globally. Since 2020, this regimen has been implemented at the American University of Beirut Medical Center (AUBMC) for patients ineligible for intensive chemotherapy.

: This study evaluates its efficacy and safety in newly diagnosed and relapsed/refractory (R/R) AML. We retrospectively analyzed consecutive AML patients treated with CLAD-LDAC-venetoclax between January 2020 and September 2024. Treatment consisted of cladribine (5 mg/m²/day, 5 days), LDAC (20 mg subcutaneously twice daily, 10 days), and venetoclax (100 mg daily with azole antifungal co-administration). Outcomes are overall response rate (ORR), including complete remission (CR), and CR with incomplete hematologic recovery (CRi), event-free survival (EFS), overall survival (OS), and safety.

: Among 19 frontline patients (median age: 67 years), the ORR was 88% (CR/CRi: 76%/12%), with 47% undergoing allogeneic hematopoietic cell transplantation (allo-HCT). Median EFS was 13.4 months, OS was 35.3 months, and 2-year OS was 58%. In 14 R/R AML patients (all venetoclax-pretreated), ORR was 57% (CR/CRi: 29%/21%), with a median EFS of 2 months and OS of 5.2 months. In both cohorts, infection rates were increased, especially in secondary AML.

: CLAD-LDAC-venetoclax was highly effective in newly diagnosed AML, but had limited response durability in the R/R setting, particularly post-venetoclax exposure. These findings support its role as an induction strategy for unfit patients and highlight the need for novel salvage approaches in R/R AML.