Aspacytarabine for the treatment of patients with AML unfit for intensive chemotherapy: a phase 2 study.

Overview

High-dose cytarabine is associated with gastrointestinal and cerebellar toxicity precluding its use in older or unfit patients with acute myeloid leukemia (AML). Aspacytarabine, an inactive prodrug of cytarabine, was evaluated as monotherapy in a phase 2b study, in patients with AML unfit for intensive chemotherapy (NCT03435848). Sixty-five patients with AML were treated with aspacytarabine 4.5 g/m2/d (equimolar to 3 g/m2/d cytarabine) for 6 doses per treatment courses. The median age was 75 years; 60.6% had de novo AML, 28.8% had AML secondary to myelodysplastic syndrome and 10.6% therapy-related AML. Overall, 36.9% achieved complete remission (CR) with full count recovery. CR rates in patients with secondary AML, patients with prior treatment with hypomethylating agents and patients with TP53-mutation were 26.7%, 25%, and 36%, respectively. Median overall survival was 9 months (range 6 to 15.9) and not reached among responders. Hematologic recovery was observed in all responding patients by day 26 with no prolonged cytopenias. Adverse events typically precluding the use of high-dose cytarabine in older or unfit patients were not observed. Aspacytarabine appears to be an effective regimen, with a reduction in the attendant toxicities associated with high-dose cytarabine, an important consideration when treating AML and other hematologic disorders that use high-dose cytarabine.