J Clin Oncol: Eprenetapopt combined with Aza cytosine to treat TP53 mutant MDS and AML

Regardless of the treatment, the prognostics of TP53 mutation (TP53m) bone marrow prognostic abnormal syndrome (MDS) and acute myeloid leukemia (AML) were very poor, with only 40% remission rate (full remission rate of 20%) for Azatide (AZA) monotherapy (CR) and short remission duration, with a medium total survival period (OS) of approximately 6 months.
Eprenetapopt (APR-246) is a new class of drugs that reconstruct the p53 protein and reactivate its function of promoting apoptosis and cell cycle blocking.
study is a clinical trial II designed to assess the safety and effectiveness of Eprenetapopt combined with AZA for untreated patients with TP53m MDS and AML in untreated high or very high international prognostic scoring system R.
52 TP53m patients (34 MDS, 18 AML) were recruited for the TP53 mutation at the baseline of all patients.
in MDS patients, the total remission rate (ORR) was 62%, including 47% CR, and the medium remission duration was 10.4 months.
33% of patients with AML, including 17% of CR.
patients with 73% of the associated cell mutations received TP53 second-generation sequencing negative (e.g. variant allegen frequency -lt;5%).
the main therapeutic-related adverse reactions were a decrease in fever-neutral granulocytes (36%) and neurological adverse events (40%), which were associated with a lower rate of renal cytofiltration (P -lt;0.01) and an older age (P -0.05) at the beginning of treatment;
9.7 months of post-prognostic follow-up, MDS patients had a mid-OS of 12.1 months, and AML patients had 3.0 months of OS.
all, in very high-risk TP53m MDS and AML patients, Eprenetapopt's joint solution with AZA is safe, demonstrating higher ORR and CR rates and longer OSs than AZA alone.