Among patients with TP53-mutated acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS), adding eprenetapopt (APR-246) to maintenance azacitidine after hematopoietic stem cell transplantation (HCT) appears both safe and effective, according to research presented at the 2022 Tandem Meetings.

Patients with TP53-mutant AML or MDS have few treatment options, and allogeneic HCT is the only therapy currently linked with curative potential. Maintenance therapy after HCT, including azacitidine, however, does not typically improve outcomes.

Eprenetapopt is a small molecule that stabilizes p53 proteins, and research suggests that it may work in tandem with azacitidine to promote cancer cell death. For this phase 2 study, researchers evaluated the safety and efficacy of adding eprenetapopt to maintenance azacitidine among patients with TP53-mutant AML or MDS who undergo HCT.

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Overall, 33 patients were enrolled and received maintenance therapy per this protocol. Nineteen patients had MDS, while 14 had AML; the median patient age, overall, was 65 years, 64% of patients were male sex, 97% had TP53 mutations, and 82% had complex cytogenetics.

The median relapse-free survival (RFS) follow-up period was 413 days. At this point, the median RFS was 368 days (95% CI: 233-not evaluable), and the 1-year RFS rate was 59.9%. The median overall survival was 586 days (95% CI: 369-not evaluable), and the 1-year overall survival rate was 79%. As of June 2021, 18% remained on study treatment; 9 had completed 12 cycles.

Grade 3 or worse treatment-related adverse events occurring in at least 10% of patients included cytopenias and hypertension. A total of 13 patients developed acute or chronic graft vs host disease.

Asmita Mishra, MD, of the H. Lee Moffitt Cancer Center and Research Institute in Tampa, Florida, who presented the study’s findings, noted that outcomes were “substantially improved over historical data.”

Disclosure: The study author(s) declared affiliations with biotech, pharmaceutical, or device companies. Please see the original reference for a full list of authors’ disclosures. 

Read more of Hematology Advisor’s coverage of the 2022 Tandem Meetings by visiting the conference page.


Mishra A, Tamari R, Byrne M, et al. Phase II trial of eprenetapopt (APR-246) in combination with azacitidine (AZA) as maintenance therapy for TP53 mutated acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS) following allogeneic hematopoietic cell transplantation (HCT). Presented at: 2022 Tandem Meetings; April 23-26, 2022. Abstract 39.