Eprenetapopt Plus Azacitidine Shows Potential After Allogeneic HSCT for TP53-Mutated MDS, AML

A phase II, multicenter, open-label trial found that eprenetapopt plus azacitidine was well tolerated and safe and has the potential to improve outcomes as maintenance therapy after allogeneic hematopoietic stem cell transplantation (HSCT) for patients with TP53-mutated acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS).

The results were published in the Journal of Clinical Oncology in a paper by Asmita Mishra, MD, of the H. Lee Moffitt Cancer Center and Research Institute in Tampa, Florida, and colleagues.

Eprenetapopt (APR-246) is a first-in-class, small-molecule p53 reactivator. In previous research, eprenetapopt had demonstrated preclinical synergistic activity with azacitidine, and the combination had shown efficacy and safety in clinical trials of TP53-mutated myeloid malignancies.

The current study investigated the combination on patients with TP53-mutated AML and MDS, a high-risk population that generally faces poor outcomes even after allogeneic HSCT.

Among 84 patients screened, 55 underwent allogeneic HSCT, and 33 received maintenance therapy (14 AML and 19 MDS). Patients with TP53-mutated MDS or AML received up to 12 cycles of eprenetapopt 3.7 g once daily intravenously on days one to four and azacitidine 36 mg/m² once daily intravenously or subcutaneously on days one to five in 28-day cycles.

The median patient age was 65 years (range, 40-74 years), and the median number of eprenetapopt cycles given was seven (range 1-12 cycles).

The results showed that the combination was well tolerated with acceptable safety. With a median follow-up of 17.0 months, the median overall survival (OS) was 20.6 months, and the one-year OS probability was 78.8%. The median relapse-free survival (RFS) was 12.5 months, and the one-year RFS was 59.9%

“Maintenance therapy with the eprenetapopt and azacitidine combination has the potential to improve post-[HSCT] outcomes in patients with [TP53-mutated] AML or MDS,” the authors wrote.

Mishra A, Tamari R, DeZern AE, et al. Eprenetapopt plus azacitidine after allogeneic hematopoietic stem-cell transplantation for TP53-mutant acute myeloid leukemia and myelodysplastic syndromes. J Clin Oncol. 2022. doi:10.1200/JCO.22.00181