Combination maintenance therapy improves survival in TP53-deficient AML post-HSCT

August 2022 Clinical practice Nalinee Pathak
blood smear is often used as a follow-up test to abnormal results on a complete blood count (CBC) to evaluate the different types of blood cells.Medical science background showing blast cells(AML)

Recent updates from a phase-II study suggest that combining eprenetapopt plus azacitidine with maintenance therapy post hematopoietic stem cell transplantation (HSCT) improves survival outcomes in acute myeloid leukaemia (AML) patients lacking TP53. These findings were published in the Journal of Clinical Oncology.

TP53 is a well-known tumour suppressor mutated in around 20% of patients with AML or myelodysplastic syndrome (MDS).  Despite the available standard of care (maintenance therapy), TP53-deficient patients have poorer clinical outcomes.

Pre-clinical studies have demonstrated that Eprenetapopt, a p53 stabiliser, synergises with azacitidine, reducing proliferation and increasing apoptosis. Based on these encouraging results, the combination was evaluated for its efficacy in a clinical study.

Study Design

The multicentre, phase-II, open-label trial enrolled 33 patients with either TP53-mutant AML (n = 14) or TP53-mutant MDS (n = 19). All the participants received a combination of eprenetapopt plus azacitidine as maintenance therapy post-HSCT. The study’s primary endpoint (RFS) was the time from HSCT to relapse or death, whereas the secondary endpoints included overall survival (OS), mortality rate and incidence of graft-versus-host disease.

Main findings

After a median follow-up of 14.5 months, the researchers reported a median RFS of 12.5 months (95% CI, 9.6 to not estimable) and OS of 20.6 months (95% CI, 14.2 to not estimable) in patients administered maintenance therapy post-HSCT.  Both drugs were well tolerated, with acceptable safety profiles. Most common grade 3 adverse events included pyrexia (12%), febrile neutropenia (6%) and dyspnea (6%).


The results of the phase-II study are highly promising and support future treatment-control studies for evaluating the clinical efficacy of the combination maintenance therapy for TP53-AML or MDS patients.


Mishra A, et al. J Clin Oncol. 2022;doi:10.1200/JCO.22.00181