# Association between gene mutations and outcomes in Japanese high-risk AML patients: a phase 1/2 study of NS-87/CPX-351

## TL;DR

This study examined gene mutations in Japanese high-risk AML patients treated with NS-87/CPX-351 and found no direct link between mutations and treatment response, but TP53 mutations were associated with higher relapse risk.

## Contribution

The study identifies TP53 mutations as a risk factor for relapse in AML patients treated with NS-87/CPX-351, despite similar remission rates.

## Key findings

- TP53 mutations were associated with shorter survival and relapse-free periods despite similar remission rates.
- No gene mutations directly influenced the efficacy of NS-87/CPX-351 in achieving remission.
- Patients with TP53 mutations may benefit from early transplantation after remission to reduce relapse risk.

## Abstract

This phase 1/2 study investigated the association between genetic characteristics and outcomes for NS-87/CPX-351 in Japanese patients with high-risk acute myeloid leukemia. Blood samples collected from 29 patients were analyzed using a 70-gene next-generation sequencing panel. The most frequently mutated genes were TP53 (44.8%), TET2 (24.1%), DNMT3A (13.8%), and NRAS (13.8%). The rates of composite complete remission (CRc; complete remission [CR] or CR with incomplete hematologic recovery [CRi]) were comparable between patients with and without mutations in TP53, TET2, DNMT3A, and NRAS (P = 0.571 for all). Notably, patients with TP53 mutations had a similar CRc rate (69.2% vs. 56.3%), but shorter overall survival (OS), event-free survival (EFS), and relapse-free survival (RFS) compared to patients with wild-type TP53 (median OS: 7.43 vs. 18.18 months; P = 0.108, median EFS: 2.43 vs. 6.28 months; P = 0.012, median RFS: 1.48 vs. 10.19 months; P = 0.012). In conclusion, no gene mutations directly associated with the efficacy of NS-87/CPX-351 were found. While NS-87/CPX-351 achieved remission even in patients with TP53 mutations, relapse risk was higher in these patients. Therefore, it is advisable to consider treatment strategies such as early transplantation after achieving remission with NS-87/CPX-351, especially in patients with TP53 mutations.

The online version contains supplementary material available at 10.1007/s12185-025-03956-8.