Aspacytarabine May Be Viable Option for Patients with AML Who Are Unfit for Intensive Therapy


Recently presented findings demonstrate that aspacytarabine may represent a viable treatment option for various subsets of patients with acute myeloid leukemia.

Jessica Altman, MD

Jessica Altman, MD

Aspacytarabine (BST-236), a novel antimetabolite, induced encouraging response rates in adult patients with newly diagnosed acute myeloid leukemia (AML) who are unfit for intensive therapy, according to data from a phase 2b trial (NCT03435848).1

Findings presented during the 2021 ASH Annual Meeting showed that the agent produced a complete remission (CR) of 37% overall, 44% in patients with de novo AML (n = 39), 35% in those aged 75 years or older (n = 34), 32% in those with an ECOG performance status of 2 or higher (n = 25), 32% in those with an adverse European LeukemiaNet (ELN) score (n = 34), 27% in those who previously received hypomethylating agents (HMAs; n = 11), and 27% in those who had secondary AML (n = 26).2

“These final CR data are extremely encouraging and strengthen our conviction in the potential of aspacytarabine as a potential standard-of-care treatment option for [patients with] AML,” Jessica Altman, MD, lead study investigator and professor of medicine in the Hematology Oncology Division of the Feinberg School of Medicine, Robert H. Lurie Comprehensive Cancer Center of Northwestern University, stated in a press release. “Notably, a CR rate of 37% was achieved in a challenging patient population, including [those] with secondary AML, prior HMA treatment, and older age.”

The novel proprietary antimetabolite is comprised of cytarabine that is covalently bound to asparagine, acting as a prodrug of cytarabine, which has served as a backbone of therapy in this disease for over 4 decades. Although strong efficacy can be achieved with cytarabine, the agent is also linked with severe bone marrow, gastrointestinal, and neurological adverse effects (AEs).

Aspacytarabine has been shown to have unique pharmacokinetics and metabolism which allows for high-dose treatment with less systemic exposure to free cytarabine as well as sparing normal tissues. For these reasons, investigators hypothesize that aspacytarabine may represent a superior option for AML and other malignancies.

For the phase 2 trial, investigators set out to examine the safety and efficacy of single-agent aspacytarabine as induction and consolidation treatment in patients with newly diagnosed AML who were not eligible to received standard induction chemotherapy. Those with secondary or therapy-related AML and those who previously received a HMA with or without venetoclax (Venclexta) for a preceding condition were permitted.

Study participants received aspacytarabine at 4.5 g/m2 per day, equimolar to 3 g/m2 per day of cytarabine. The agent was given via daily 1-hour infusions as part of 6-day courses for 1 to 2 induction courses and 1 to 3 consolidation courses.

The primary end point of the trial was CR, and key secondary end points included safety, overall survival (OS), duration of response (DOR), and minimal residual disease (MRD).

The median age of study participants (n = 65) was 75 years (range, 54-88), and 52% of patients were 75 years or older. Moreover, 62% of patients had an ECOG performance status of 0 or 1 and 38% had a status of 2 or 3. Additionally, 40% of patients had secondary AML, 29% of whom had disease secondary to myelodysplastic syndrome or chronic myelomonocytic leukemia and 11% of whom had disease secondary to therapy.

Seventeen percent of patients previously received an HMA. Moreover, 34% of patients had a bone marrow blast percentage of less than 30%, 25% had a percentage ranging from 30% to 50%, and 41% had a percentage of greater than 50%. Most patients (52%) had an adverse ELN risk score; 25% had an intermediate score, 14% had a favorable score, and 9% did not have this information available.

The data cutoff date for the analysis presented during the meeting was December 2021.

Additional findings from the trial revealed that CRs were reached after 1 to 2 courses of induction treatment, and 50% of those who achieved the CRs were MRD negative. The median DOR with the agent was 6.0 months (95% CI, 3.9–not reached).

Rapid complete hematological recovery was reported in all patients who achieved a complete bone marrow response, with a median time of 25 days (range, 11-39) for complete neutrophil recovery, and 26 days (range, 18-40) for complete platelet recovery.

Follow-up for the median DOR and OS is ongoing.

Regarding safety, the treatment-emergent AEs that were grade 3 or higher and were most frequently reported with the agent included febrile neutropenia (50%), thrombocytopenia (27%), anemia (21%), leukopenia (21%), hypokalemia (18%), sepsis (15%), neutropenia (14%), pneumonia (14%), hypophosphatemia (11%), and hypoxia (11%).

Related serious AEs included febrile neutropenia (9%), sepsis (6%), pneumonia (5%), thrombocytopenia (5%), and anemia (3%).

In August 2020, the FDA granted a fast-track designation to aspacytarabine for use in patients with AML who are aged 75 years and older and who have comorbidities that preclude the utilization of intensive induction chemotherapy.3


  1. Biosight reports final primary endpoint data from phase 2b study of aspacytarabine (BST-236) for first-line acute myeloid leukemia therapy. News release. BioSight Ltd.; January 6, 2022. Accessed January 10, 2022.
  2. Altman JK, Koprivnikar J, McCloskey JK, et al. Aspacytarabine (BST-236) as monotherapy is safe, well-tolerated and effective for the treatment of adults with newly diagnosed acute myeloid unfit for intensive therapy. Results of a phase 2 study. Blood. 2021;138(suppl 1):1273. doi:10.1182/blood-2021-149361
  3. Biosight granted US FDA fast track designation for BST-236 for the treatment of acute myeloid leukemia. News release. Biosight Ltd; August 4, 2020. Accessed January 10, 2022.

This article was originally published on OncLive as “Aspacytarabine Shows Efficacy, Safety in Newly Diagnosed AML Unfit for Intensive Therapy”

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