Prognostic impact of MRG mutations in FLT3‑ITD AML: HARMONY analysis

Results from an analysis of the HARMONY platform, assessing the prognostic impact of myelodysplasia-related gene (MRG) mutations in adults with FLT3-internal tandem duplication (ITD) acute myeloid leukemia (AML), were published in Leukemia by Mecklenbrauck et al. Patients who had been treated with intensive chemotherapy (IC), and for whom the mutational status of FLT3, NPM1, and nine MRG mutations were available, were included (N = 862).

Key data: Of 862 patients with FLT3‑ITD AML, 20% (n = 171) exhibited co-occurring MRG mutations at diagnosis. In the overall FLT3‑ITD cohort, MRG status was not independently associated with overall survival (OS; multivariable hazard ratio [HR], 1.14; 95% confidence interval [CI], 0.92–1.42; p = 0.20) or relapse-free survival (RFS; univariate HR, 1.15; 95% CI, 0.90–1.46; p = 0.30). MRG mutations were present in 34% of all patients with FLT3‑ITD/NPM1-wildtype AML; in multivariable analysis, MRG mutations independently predicted shorter OS (HR, 1.34; 95% CI, 1.02–1.74; p = 0.032) and RFS (HR, 1.37; 95% CI, 1.01–1.88; p = 0.046) . In patients with FLT3‑ITD/NPM1-mutated AML, MRG mutations were rare (9%) and showed no independent prognostic impact for OS or RFS.

Key learning: Results indicate that the prognostic relevance of MRG mutations in FLT3‑ITD AML is modulated by NPM1 co-mutational status, supporting a more nuanced approach to genetic risk stratification in this setting.