Eprenetapopt/Azacitidine Maintenance After Allogeneic HSCT for TP53-Mutant AML and MDS

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In a phase II trial reported in the Journal of Clinical Oncology, Mishra et al found that maintenance treatment with the first-in-class small-molecule p53 reactivator eprenetapopt plus azacitidine following allogeneic hematopoietic stem cell transplantation (HSCT) was associated with “encouraging” outcomes in patients with TP53-mutant acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS).

Study Details

The multicenter trial enrolled patients between September 2019 and November 2020. Among 55 patients undergoing HSCT, maintenance treatment was received by 33, including 19 with MDS and 14 with AML. Among the 22 patients who did not receive maintenance treatment, 11 did not due to transplantation-related toxicity, with 2 not receiving maintenance due to early relapse. Treatment consisted of 28-day cycles of eprenetapopt at 3.7 g once daily on days 1 to 4 and azacitidine at 36 mg/m2 once daily on days 1 to 5 for up to 12 cycles. The primary efficacy outcome measure was relapse-free survival.

Relapse-Free Survival

With a median follow-up of 14.5 months, median relapse-free survival was 12.5 months (95% confidence interval [CI] = 9.6 months–not estimable), with an estimated 1-year rate of 59.9% (95% CI = 41%–74%).


  • Median relapse-free survival was 12.5 months.
  • Median overall survival was 20.6 months.

With a median follow-up of 17.0 months, median overall survival was 20.6 months (95% CI = 14.2 months–not estimable), with an estimated 1-year rate of 78.8% (95% CI = 60.6%–89.3%).

The cumulative incidence of relapse at 1 year was 38.3% (95% CI = 23.7%–57.6%) and 1-year nonrelapse mortality was 3.8% (95% CI = 0.6%–24.3%). Median time to disease progression was 15.2 months (95% CI = 9.7 months–not estimable). Median time to relapse was 9.9 months (95% CI = 5.7 months–not estimable) for patients with MDS and not estimable (95% CI = 7.7 months–not estimable) for patients with AML.

Adverse Events

Among patients receiving maintenance therapy, grade ≥ 3 adverse events occurred in 28 patients (85%) and were almost exclusively hematologic events (decreased platelets in 36%, decreased white blood cells in 36%, anemia in 27%, decreased neutrophils in 27%); a nonhematologic event was observed in 1 patient (abdominal pain). The most common serious adverse events were pyrexia (n = 4, 12%) and febrile neutropenia and dyspnea (n = 2, 6% each). Central nervous system–related effects, which have been associated with eprenetapopt, included nausea (61%), vomiting (46%), dizziness (39%), tremor (33%), headache (21%), dyskinesia (18%), and ataxia (12%), with all being grade 1 or 2.

Mortality at 30 and 60 days from first dose was 0% and 6% (2 patients), respectively; both deaths were due to disease progression. Any-grade acute and chronic graft-vs-host disease was observed in 4 patients (12%) and 11 patients (33%; grade 3 in 2 patients), respectively.

The investigators concluded: “In patients with [mutant] TP53 AML and MDS, post-HSCT maintenance therapy with eprenetapopt combined with azacitidine was well tolerated. Recurrence-free survival and overall survival outcomes were encouraging in this high-risk population.”

Asmita Mishra, MD, of the Department of Blood and Marrow Transplant and Cellular Immunotherapy, H. Lee Moffitt Cancer Center and Research Institute, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was funded by Aprea Therapeutics. For full disclosures of the study authors, visit

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