The following is a summary of “Eprenetapopt Plus Azacitidine After Allogeneic Hematopoietic Stem-Cell Transplantation for TP53-Mutant Acute Myeloid Leukemia and Myelodysplastic Syndromes,” published in the December 2022 issue of Oncology by Mishra, et al.

Even after an allogeneic hematopoietic stem-cell transplant (HCT), the prognosis for patients with TP53-mutant (mTP53) acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) is dismal. An innovative small-molecule p53 reactivator is eprenetapopt (APR-246).

For a study, researchers sought to determine the effectiveness and safety of using eprenetapopt in combination with azacitidine as a maintenance treatment following HCT. They undertook a phase II, multicenter, open-label experiment. Patients with mTP53 MDS or AML were given eprenetapopt 3.7 g once daily intravenously on days 1-4 and azacitidine 36 mg/m2 once daily intravenously/subcutaneously on days 1–5 in 28-day cycles for up to 12 cycles. The key results were safety and relapse-free survival (RFS).

A transplant was performed on 55 out of the 84 individuals who underwent eligibility screenings before HCT. In the end, 33 patients (14 AML and 19 MDS) were on maintenance therapy; their ages ranged from 40 to 74, and the median was 65. Seven eprenetapopt cycles were the median number (range, 1-12). The median RFS was 12.5 months (95% CI, 9.6 to not estimable), and the 1-year RFS probability was 59.9% (95% CI, 41 to 74). With a 17.0-month median follow-up, the 1-year OS probability was 78.8% (95% CI, 60.6 to 89.3), and the median overall survival (OS) was 20.6 months (95% CI, 14.2 to not estimable). Mortalities at 30 and 60 days following the first dosage were 0% and 6%, respectively (n = 2). Adverse events associated with acute and chronic (all grade) graft-versus-host and disease was documented in 12% (n = 4) and 33% (n = 11) of patients, respectively.

Eprenetapopt and azacitidine post-HCT maintenance treatment was well tolerated in individuals with mTP53 AML and MDS. The RFS and OS results in the high-risk cohort were positive.