Cladribine With Low‐Dose Cytarabine and Venetoclax Alternating With Azacitidine and Venetoclax for Newly Diagnosed Acute Myeloid Leukemia

ABSTRACT Venetoclax‐based low‐intensity regimens have improved the outcomes of older or unfit patients with acute myeloid leukemia (AML). This phase II study investigated the combination of cladribine plus low‐dose cytarabine and venetoclax alternating with azacitidine plus venetoclax for older or unfit patients with newly diagnosed AML. A total of 190 patients were included; the median age was 68 years (range, 47–84 years; 13% ≥ 75 years). By the European LeukemiaNet 2022 classification, 16%, 20%, and 64% were stratified as favorable, intermediate, and adverse risk, respectively. The rates of complete remission (CR)/CR with incomplete blood count recovery (CRi) and minimal residual disease (MRD) negative CR/CRi were 84% and 75% overall and 91% and 77% among patients with TP53 ‐wild type AML, respectively. The 4‐ and 8‐week mortality rates were 1% and 3%, respectively. Among responders, 44% proceeded to allogeneic hematopoietic stem cell transplantation. The median overall survival (OS) and event free survival (EFS) were 52 and 50 months, respectively. The 2‐ and 5‐year OS rates were 60% and 45%, respectively. The 2‐and 5‐year EFS rates were 56% and 43%, respectively. Patients achieving MRD‐negative CR had a median OS not reached and a 2‐year OS rate of 70%. The median time to absolute neutrophil count recovery (> 1 × 10 9 /L) and platelet count recovery (> 100 × 10 9 /L) after induction was 27 and 24 days, respectively. Overall, the treatment was safe and most grade 3 and 4 adverse events were infectious complications. The combination produced a high rate of remissions, translating into favorable outcomes for older patients with newly diagnosed AML. Trial Registration: ClinicalTrials.gov idetifier: NCT03586609