Aspacytarabine Safe and Effective in Patients with AML Unfit for Intensive Chemotherapy

According to results from a clinical trial presented during the American Society of Clinical Oncology 2021 virtual annual meeting, aspacytarabine (BST-236), a prodrug of cytarabine, appears safe and effective as first-line therapy for patients with acute myeloid leukemia (AML) who are unfit for intensive chemotherapy.

“These data could establish aspacytarabine as a new, tolerable AML chemotherapy backbone for this challenging patient population,” said lead investigator Jessica K. Altman, MD, Professor, Hematology and Oncology, Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, IL.

According to Dr Altman, the standard of care for newly diagnosed AML is intensive chemotherapy with cytarabine, which is associated with toxicities that limit its applicability in many older adults and in those with significant comorbidities. For adults not appropriate for intensive therapy, the use of hypomethylating agents with venetoclax (Venclexta) has changed the treatment landscape, but there are relatively limited data on adults with traditionally poor prognostic features who were previously treated with these agents.

“Despite recent [treatment] advances, there is a need for more effective and less toxic chemotherapy approaches,” she said

Deep and Durable Responses

The phase 2b, open-label study enrolled 46 patients with newly diagnosed AML who were unfit for standard chemotherapy. Patients received 4.5 g/m2 daily of aspacytarabine in 1 to 2 induction courses and 1 to 3 consolidation courses.

The median patient age was 75 years; 63% of patients had de novo AML, and the remaining had secondary AML. Six (13%) patients had received previous hypomethylating agents with or without venetoclax for the treatment of their underlying myeloid neoplasm.

As of April 19, 2021, 39% of patients had achieved complete response (CR), including those who had received previous hypomethylating agents.

“If we limit the analysis to those patients who had not received previous hypomethylating agent-based therapy, the CR rate is 45%, and median number of cycles to achieve a CR is 1,” said Dr Altman, who added that all responding patients have had normalization of blood counts. “The median duration of response is not yet reached at 12 months.”

Complete hematologic recovery occurred within 28 days following induction/reinduction, and the median time to platelet recovery after induction was 26 days.

Median time to absolute neutrophil count recovery and platelet recovery following consolidation cycles was 15 days and 23 days, respectively, which is a shorter time than seen after induction, said Dr Altman.

Results also showed that 63% of patients who achieved CR were minimal residual disease (MRD)-negative. In the overall cohort, 23% of patients had an MRD-negative CR. This rate improved to 26% when the analysis was limited to patients who received no previous hypomethylating agent.

Median overall survival (OS) for all patients treated in the study was 10 months and the median OS for patients with secondary AML was 6.8 months. The median OS for adults with de novo AML and for patients who had a CR, had not been reached at the time of the presentation.

Safety Profile

Treatment-related adverse events (≥20%) included febrile neutropenia (57.4%), hypokalemia (44.7%), and peripheral edema (42.6%); notable grade ≥3 treatment-related adverse events included febrile neutropenia (48.9%) and thrombocytopenia (38.2%). Dr Altman noted that these toxicities were typical among older adults with AML.

Future Trials

“Based on this work, additional trials are being initiated, including a single-agent study being conducted in Europe and the United States with aspacytarabine for the treatment of relapsed and refractory myelodysplastic syndromes and AML,” Dr Altman said. “In addition, another front-line AML study is being initiated for those adults deemed unfit for intensive therapy, combining aspacytarabine with venetoclax and induction, and patients will receive aspacytarabine alone and in consolidation.”

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