Clofarabine and intermediate-dose cytarabine after venetoclax failure in relapsed/refractory acute myeloid leukemia: a retrospective single-center experience

Abstract Background Resistance to venetoclax (VEN)-based therapies is a therapeutic challenge in acute myeloid leukemia (AML). Objectives To evaluate the efficacy of clofarabine in combination with intermediate-dose cytarabine in patients with VEN-resistant AML. Methods Two real-world cohorts of relapse/refractory (R/R) adult AML patients: a VEN-failure cohort (n = 9) and a pre-VEN cohort (n = 33). Patients received clofarabine 22.5 mg/m²/day and cytarabine 1 g/m²/day D1-5. Results In the VEN-failure cohort 11% of patients achieved partial response (PR), 89% were refractory (ORR 11%). The median OS was 2.0 months. Early mortality occurred in 33% of patients. In the pre-VEN cohort 33% of patients achieved complete remission, 6% PR (ORR 39%). The median OS was 4.0 months. Early mortality was recorded in 3% of patients. Conclusions In this limited, retrospective single-center experience, clofarabine plus intermediate-dose cytarabine showed minimal clinical activity and an unfavorable early toxicity profile in VEN-exposed R/R AML patients.