Health

First-Line Aspacytarabine Meets Efficacy Mark in ‘Challenging’ AML Patients

Single-agent aspacytarabine as first-line therapy was effective and safe in patients with acute myeloid leukemia (AML) who were not fit for intensive chemotherapy, a researcher reported.

In a phase II study, treatment with the agent achieved a 39% complete remission (CR) rate in the study population, with a safety profile that was “on target,” according to Jessica Altman, MD, of the Lurie Comprehensive Cancer Center at Northwestern University in Chicago.

“Aspacytarabine has the potential to be a treatment strategy for this challenging patient population,” Altman said in a presentation at the American Society of Clinical Oncology virtual meeting.

While treatment advances have had a significant impact on AML patients, Altman explained that the majority of patients still suffer from relapse and eventually die of the disease. While the standard of care for this population is intensive chemotherapy, including cytarabine, this regimen is associated with toxicity that limits its applicability in many older adults and those with significant comorbidities, she said, adding that “There is a need for more effective and less toxic chemotherapy approaches.”

Aspacytarabine is a cytarabine prodrug, which is inactive and nontoxic until metabolized to cytarabine. It gradually releases cytarabine over the course of an 8-hour period, and requires a 1-hour infusion, which is substantially shorter than the 3-hour infusion of high-dose cytarabine. This gradual release of cytarabine, Altman pointed out, reduces systemic exposure to peak, toxic cytarabine levels and limits damage to normal tissues.

In the open-label, single-arm, multicenter study, Altman and colleagues assessed the efficacy and safety of aspacytarabine in adults with newly diagnosed AML who were not eligible for standard induction therapy.

As of April 21, 2021, 60 patients were enrolled in the study, with 46 patients (median age 75) evaluable for analysis. These patients completed one to four courses of 4.5 g/m2/d aspacytarabine (containing 3 g/m2/d cytarabine).

Patients with secondary AML, prior hypomethylating agent (HMA) therapy, and therapy-related AML, were eligible for the study. The study’s primary efficacy endpoint was CR. The researchers found that 39% of patients achieved CR, while CR was achieved by 45% in patients who had not previously received HMA therapy. The median number of cycles needed to achieve CR was one.

The median duration of response was not reached at 12 months. All responding patients had normalization of blood counts within 28 days.

As for safety, Altman and colleagues reported that adverse events were as expected with aspacytarabine, and they noted that no cerebellar toxicity or mucositis has been reported in the patient population.

In addition, 63% of patients who had CR were negative for minimal residual disease (MRD). In the entire study population, 23% of patients with CR were MRD negative, including patients with prior HMA. If those patients are excluded, the MRD-negative rate was 26%.

Median overall survival (OS) for the entire cohort was 10 months. The median OS for patients with secondary AML was 6.8 months, and was not reached in patients with de novo AML. Patients who did not achieve a CR had a median OS of 6.1 months, while median OS was not reached for patients who achieved a CR.

Altman said additional trials are being initiated based on results from this study, including a single-agent study with aspacytarabine in relapsed/refractory AML and myelodysplastic syndromes, as well as study of aspacytarabine in combination with venetoclax (Venclexta).

“This study elegantly highlights that there is still a role for chemotherapy in the management of AML, even in the era of targeted agents,” commented Guru Murthy, MD, of the Medical College of Wisconsin in Wauwatosa. He suggested that future larger studies will be helpful proving aspacytarabine’s efficacy and safety.

“An attractive aspect of this agent is the fixed duration of therapy compared to other agents, such as hypomethylating agent therapy, venetoclax, and IDH1 and 2 inhibitors,” Murthy noted, adding that these agents are used continuously until disease progression “which can result in treatment-related and financial toxicities for the patient.”

Developer Biosight announced in May that enrollment for a phase IIb trial was complete. Aspacytarabine was granted FDA Fast Track Designation for first-line treatment of AML patients unfit for standard chemotherapy, and Orphan Drug designations from the FDA and the European Medicines Agency, according to Biosight.

  • Mike Bassett is a staff writer focusing on oncology and hematology. He is based in Massachusetts.

Disclosures

The study was funded by Biosight. Some co-authors are company employees.

Altman disclosed relationships with, and/or support from AbbVie, Agios, Astellas Pharma, Biosight, GlycoMimetics, Kura Oncology, Syros Pharmaceuticals, Theradex, Abbvie (institutional), Agios (institutional), Ambit BioSciences (institutional), Amgen (institutional), Amphivena (institutional), Aprea AB (institutional), ARIAD (institutional), Astellas Pharma (institutional), Astex Pharmaceuticals (institutional), BiolineRx (institutional), Biosight (institutional), Boehringer Ingelheim (institutional), Bristol-Myers Squibb (institutional), Celgene (institutional), Cyclacel (institutional), Fujifilm (institutional), Kartos Therapeutics (institutional), Kura Oncology (institutional), MethylGene (institutional), Pfizer (institutional), Spectrum Pharmaceuticals (institutional), and Daiichi Sankyo.

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