GIMEMA AML1310: Sex-stratified differences in de novo AML

A sex-stratified analysis of the Gruppo Italiano Malattie EMatologiche dell’Adulto (GIMEMA) AML1310 trial (NCT01452646), investigating the impact of sex differences on disease features and outcomes in patients with de novo acute myeloid leukemia (AML; N = 500), was published in the American Journal of Hematology by Melillo et al. Mutational profiling, cytogenetic, and outcome analyses stratified by sex were undertaken in patients who received post-consolidation therapy with autologous hematopoietic stem cell transplantation (auto-HSCT) or allogeneic hematopoietic stem cell transplantation (allo-HSCT) based on their risk profile.

Key data: Of the overall population, 52% were male and 48% were female. At a median follow-up of 6.4 years, overall survival (OS) for the whole cohort was 42.7% (95% confidence interval [CI], 38.3–47.6) and did not differ between sexes (39.4% vs 46% for males and females, respectively; p = 0.218). Female patients with NPM1 mutations demonstrated superior 6-year OS (52.4% vs 33.8%; p = 0.032), disease-free survival (DFS; 47% vs 35%; p = 0.085), and improved survival among patients with measurable residual disease (MRD) positivity after consolidation (66.5% vs 45%; p = 0.015) compared with male patients. OS at 6 years was greater following auto-HSCT compared with allo-HSCT (67.4% vs 50.6%; p = 0.007), with female patients demonstrating the greatest benefit compared with male patients (p = 0.032). 

Key learning: Results suggest that sex-based differences significantly influence treatment outcomes in patients with AML, particularly among patients with NPM1 mutations, highlighting the value of incorporating sex-stratified analyses into AML clinical trials to enhance personalized treatment approaches.