A regimen of cladribine plus low-dose cytarabine plus venetoclax alternated with 5-azacytidine plus venetoclax showed encouraging efficacy in patients with newly diagnosed acute myeloid leukemia (AML). Moreover, the displayed efficacy was consistent across European LeukemiaNet (ELN) risk groups and patients ≥70 years of age. The results of this phase 2 trial need to be confirmed in larger trials [1].

Dr. Patrick Reville (MD Anderson Cancer Center, TX, USA) and colleagues included patients with newly diagnosed AML of ≥60 years of age to evaluate a regimen of cladribine plus low-dose cytarabine plus venetoclax, alternating with 5-azacytidine plus venetoclax. Participants (n=60) followed 1 or 2 cycles (28 days per cycle) of induction therapy (cladribine, 5 mg/m2, once daily on day 1 to 5; cytarabine, 20 mg, twice daily on day 1 to 10; venetoclax, 100 mg, 200 mg, or 400 mg [dose depending on the use of CYP3A4 inhibitors], for 21 days). Subsequently, they received 2 cycles of 5-azacytidine (75 mg/m2) on days 1 to 7 and venetoclax on the first 7 to 14 days, depending on measurable residual disease and tolerability. Hereafter, 2 cycles of maintenance cladribine, low-dose cytarabine, and venetoclax were alternated with 2 cycles of 5-azacytidine plus venetoclax, up to 18 cycles. The primary outcome was a composite complete response (CR/CRi) rate. In total, 93% of the patients achieved the composite CR rate, with 80% of the patients reaching CR and 13% of the patients achieving CRi. Early mortality rates were low, with 1 deceased patient after 4 weeks and 4 mortalities after 8 weeks. The observed response rate was consistent across subgroups: ELN Adverse (96%), Adverse/Complex Cytogenetics (89%), FLT3-mutated (88%), MLL-rearranged (75%), and secondary AML (93%). The disease-free survival (DFS) rate was 60% after 24 months; median DFS was not yet reached. Similarly, median event-free survival and median overall survival were not yet reached after 24 months, with rates of 56% and 64%, respectively. The rate of serious adverse events was low. Febrile neutropenia (55%) and pneumonia (23%) were the most common grade 3 events. Tumor lysis syndrome was observed in 1 patient.

  1. Reville PK, et al. Phase II Study of Venetoclax Added to Cladribine (CLAD) and Low Dose AraC (LDAC) Alternating with 5-Azacytidine (AZA) in Older and Unfit patients with Newly Diagnosed Acute Myeloid Leukemia (AML). O616, ASH 2021 Scientific Sessions, 11–14 December.

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