Data of aspacytarabine (BST-236), a prodrug of cytarabine, from an ongoing phase 2b study were presented at the 2021 American Society of Hematology (ASH) Annual Meeting to highlight reduced toxicity in first-line therapy for patients with acute myeloid leukemia (AML) who are unfit for intensive chemotherapy.

“Due to the pharmacokinetics and metabolism of aspacytarabine, the peak toxic systemic exposure to cytarabine is decreased, resulting in reduced systemic toxicity with relative sparing of normal tissues, thus enabling delivery of high cytarabine doses to patients with AML otherwise unfit to receive intensive cytarabine therapy,” explained Jessica Altman, MD, Northwestern University, Chicago, and co-researchers.

A total of 65 newly diagnosed patients with AML who were unfit for standard chemotherapy, with a median age of 75 years old (range, 54-88), were enrolled to the phase 2b trial and treated with aspacytarabine. Patients completed 1 to 4 courses (median 1 course) at doses of aspacytarabine 4.5 g/m² per day, including 39 patients (60%) with de novo AML and 26 patients (40%) with secondary AML.

The primary endpoint was complete remission (CR) with complete hematological recovery. Secondary and exploratory endpoints included safety, duration of response (DOR), overall survival (OS), and minimal residual disease (MRD).

Among these patients, 24 (37%) achieved a CR following 1 (17 patients) or 2 (7 patients) courses. The median time to complete neutrophil and platelet recovery was 27 days (range, 11-39 days) and 26 days (range, 18-40), respectively.

“The CR rates in de novo and secondary patients with AML were 44 percent and 27 percent, respectively. Twenty-seven percent of the patients with prior hypomethylating (HMA) therapy achieved a CR, including the 1 patient with prior HMA plus venetoclax treatment,” continued Dr Altman and co-authors.

Notably, the CR rates in patients older than 75 and patients with adverse European LeukemiaNet (ELN) scores were 35 percent and 34 percent, respectively. Further, 32 patients (49%) and 15 patients (23%) had adverse or intermediate ELN scores, respectively.

“Of the 21 patients in CR evaluable to date for MRD analysis by multiparameter flow cytometry, 11 (52%) became MRD negative following aspacytarabine treatment. Follow-up is ongoing, with a current median duration of follow-up of 5.2 months,” elaborated Dr Altman and co-researchers.

Aspacytarabine was reported to be well-tolerated during repeated-course administration. Treatment emergent adverse events (TEAEs) that were grade 3 or higher included hematological events and infections without severe gastrointestinal or neurological incidents. The 30-day all-cause mortality rate was 12.5 percent (95% CI, 5.9-23.7).

“Aspacytarabine appears to be an effective regimen for AML with a considerable reduction of the attendant toxicities that are typically associated with standard intensive cytotoxic therapies. These data support a role for aspacytarabine as a new treatment option for older patients with AML. Furthermore, this agent may serve as a backbone for combination therapy with targeted or other chemotherapy agents, as well as in younger patients with AML,” concluded Dr Altman, et al.—Alexa Stoia

Jessica A, Koprivnikar J, McCloskey J, et al. Aspacytarabine (BST-236) As Monotherapy Is Safe, Well-Tolerated for the Treatment of Adults with Newly Diagnosed Acute Myeloid Leukemia Unfit for Intensive Therapy. Results of a Phase 2 Study. Presented at: the 2021 ASH Annual Meeting; Dec. 11-14; 2021; Abstract 1273.