Posted: Wednesday, March 24, 2021
According to phase II trial findings presented in the Journal of Clinical Oncology, a combination of eprenetapopt, a novel first-in-class small-molecule also known as APR-246, and azacitidine may result in improved clinical outcomes for patients with TP53-mutated acute myeloid leukemia (AML) or myelodysplastic syndromes. Pierre Fenaux, MD, PhD, of the Groupe Francophone des Myélodysplasies in France, and colleagues found that the combination may be safe and well tolerated among a high-risk patient population.
The study included 52 patients with TP53-mutated myelodysplastic syndrome (n = 34) or AML (n = 18, 7 of whom had more than 30% blasts) classified as intermediate risk or higher. In a 28-day cycle, patients received 4,500 mg daily of intravenous eprenetapopt on days 1 to 4 plus 75 mg/m2 of daily subcutaneous azacitidine on days 4 to 10. Patients receiving maintenance treatment following allogeneic stem cell transplantation were administered 3,700 mg of daily intravenous eprenetapopt on days 1 to 4 plus 36 mg/m2 of daily subcutaneous azacitidine on days 1 to 5.
Among patients with AML, the overall response rate was 33%, with 17% achieving a complete response. A total of 27% of patients with less than 30% blasts achieved complete responses versus 0% of patients with more than 30% blasts. The overall response rate for patients with myelodysplastic syndrome was 62%, with 47% achieving a complete response and a median response duration of 10.4 months. Among all responding patients, 73% reached TP53 next-generation sequencing negativity.
At a median follow-up of 9.7 months, the median overall survival for patients with AML was 13.9 months for those with less than 30% blasts and 3.0 months for those with more than 30% blasts. The median overall survival for patients with myelodysplastic syndrome was 12.1 months.
Febrile neutropenia (36%) and neurologic adverse events (40%) were the most common treatment-related adverse events. Eprenetapopt dose reduction leading to dose interruption resolved most of the neurologic toxicity.
Disclosure: For full disclosures of the study authors, visit ascopubs.org.