Aspacytarabine Demonstrates Efficacy and Safety Benefits for Patients With AML Unfit for Intensive Chemotherapy

Findings from a Phase 2b Trial

Aspacytarabine demonstrated efficacy and safety among patients with acute myeloid leukemia (AML) who were older or unfit for intensive chemotherapy, according to a phase 2b trial published in Blood Advances. This treatment showed potential as an alternative frontline option for this patient population. 

Jessica K Altman, MD, Robert H Lurie Comprehensive Cancer Center of Northwestern University, Chicago, Illinois, and coauthors stated, “High-dose cytarabine is associated with gastrointestinal and cerebellar toxicity, precluding its use for older or unfit patients with acute myeloid leukemia.” 

To mitigate these adverse events and evaluate potential monotherapies for chemotherapy-unfit AML, the study authors aimed to assess the efficacy and safety of aspacytarabine, an inactive prodrug of cytarabine, among patients with AML who were unfit for intensive chemotherapy. 

In this trial, 65 patients with a median age of 75 years were enrolled, with 60.6% having de novo AML, 28.8% having AML secondary to myelodysplastic syndrome, and 10.6% having therapy-related AML. All patients received aspacytarabine at 4.5 g/m2 per day (equimolar to 3 g/m2 per day cytarabine) for 6 doses per treatment. 

Study results indicated that 36.9% of patients reached complete remission with full count recovery. The complete remission rate was 26.7% among patients with secondary AML, 25% among patients with prior hypomethylating agent treatment, and 36% among patients with tumor protein p53 (TP53) mutation. The median overall survival was 9 months and was not achieved among patients who responded. 

All responding patients reached hematologic recovery by day 26 without prolonged cytopenias. No adverse events that typically prevent the use of high-dose cytarabine in older or unfit patients were observed in safety analyses. 

“Collectively, given the response achieved in this study with limited treatment courses, without prolonged cytopenias after repeated administration, and a relatively favorable toxicity profile, these data suggest that aspacytarabine may provide an alternative first-line treatment option for patients with AML who are either old or otherwise unfit for [intensive chemotherapy] (IC),” Dr Altman and coauthors concluded. 

“Studies of aspacytarabine in other hematologic diseases that commonly incorporate high-dose cytarabine, such as acute lymphoblastic leukemia or lymphoma, have been proposed, and a phase 1 study combining aspacytarabine with venetoclax as induction treatment for newly diagnosed unfit patients with AML is currently ongoing,” they added.

Source: 

Altman JK, Zuckerman T, Koprivnikar J, et al. Aspacytarabine for the treatment of patients with AML unfit for intensive chemotherapy: a phase 2 study. Blood Adv. Published online: December 14, 2023. doi: doi.org/10.1182/bloodadvances.2023010943