For over one-third of older patients with acute myeloid leukemia (AML) not otherwise eligible for chemotherapy, aspacytarabine was a safe and effective first-line therapy, according to recent research presented at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting.

“The cumulative clinical data suggest that aspacytarabine, a time-limited single-agent treatment, is safe and efficacious as a first-line therapy for patients who are unfit for intensive chemotherapy, which may establish it as a new tolerable AML chemotherapy backbone,” Jessica K. Altman, MD, of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University in Chicago, and colleagues wrote in their study abstract.

Altman and colleagues evaluated results from the phase 2b ELPIS trial, where aspacytarabine was administered to 46 patients (median 75 years old) with a new diagnosis of AML, with 63% having de novo AML and 37% with secondary AML. Prior to the study, 43% of patients had an Eastern Cooperative Oncology Group (ECOG) score of 2, a median of 52% has received bone marrow blasts, 54% had an adverse-risk European LeukemiaNet (ELN) score, 29% had an intermediate-risk ELN score at baseline, and 13% of patients received a median of 12 courses of hypomethylating agents. 

Aspacytarabine was administered in 1-4 courses (4.5 g/m2 per day), which consisted of 1-2 induction courses and 1-3 consolidation courses of six 1-hour infusions per day. “Aspacytarabine is inactive in its intact prodrug form until cytarabine is gradually released at pharmacokinetics which decrease the systemic exposure to peak toxic cytarabine levels, resulting in reduced systemic toxicity and relative sparing of normal tissues, enabling therapy with high cytarabine doses to patients otherwise unfit to receive it,” the researchers explained.

Dr. Altman and colleagues found repeated administration of aspacytarabine was safe and well tolerated in their patient population, with grade 2 or higher adverse events consisting of hematologic events and infections. Overall, 15 patients (35%) in the trial achieved complete remission (CR), with 13 patients achieving CR after 1 induction course and 2 patients after 2 induction courses. Complete hematologic recovery was seen at a median of 27.5 days (range, 22-39 days). For patients with de novo AML, the CR rate was 46%, while the CR rate for patients with an adverse-risk ELN score was 33%. Eight of 11 patients (73%) in the study were minimal residual disease (MRD) negative after a MRD flow cytometry test. At 12 months and at 24 months, researchers noted that median duration of response and median overall survival was not reached.

“Aspacytarabine offers a much needed potential new treatment for older adults with AML. The limited duration of the treatment and the indicated compelling efficacy have the potential to provide key treatment advantages which may address unmet needs in poor-prognosis patient populations,” Dr. Altman stated in a press release.