KEY TAKEAWAYS
- The trial aimed to evaluate the prognostic impact of co-mutations involving NPM1 in individuals diagnosed with AML.
- The result demonstrated the less frequent pattern of co-mutational burden, potentially influencing the enhanced OS in NPM1+ AML patients and the diminished OS in NPM1– AML patients.
While the 2017 WHO classification identifies acute myeloid leukemia (AML) with NPM1 mutations as a favorable subtype, additional mutations can impact prognosis. Researchers aimed to evaluate the prognostic impact of co-mutations involving NPM1 in individuals diagnosed with AML.
Researchers aimed to evaluate the prognostic impact of co-mutations involving NPM1 in individuals diagnosed with AML. The study focussed on newly diagnosed patients with AML, idiopathic cytopenia of undetermined significance, myelodysplastic syndromes, or myelofibrosis.
For this analysis, AML patients aged ≥55 were categorized based on NPM1 status (NPM1+ vs. NPM1–), and the frequency of gene mutations was assessed in both groups. The primary outcome measure was overall survival (OS), evaluated using the Cox model adjusted for age and mutations in TP53 and RUNX1.
About 123 patients with NPM1+ AML and 360 with NPM1– AML were included, with the majority being male (NPM1+, 61.5%; NPM1–, 60.7%) and white (NPM1+, 78.0%; NPM1–, 85.6%). Median age was 67(55-87) and 71(55-97) years for NPM1+ and NPM1– groups, respectively.
After age adjustment, NPM1+ AML patients exhibited significantly longer median OS compared to NPM1– AML patients (26 vs. 15 months; HR [95% CI]: 0.58 [0.44-0.76]; P<0.01). NPM1+ AML patients had lower frequencies of key mutations, such as TP53 (1.6% vs. 18.6%) and RUNX1 (0.8% vs. 14.8%).
The initial survival advantage with NPM1+ AML, observed after age adjustment, was attenuated after further adjusting for TP53 and RUNX1 mutations (NPM1+ vs. NPM1–; 23 vs. 19 months; HR [95% CI]: 0.75 [0.48-1.17]; P=0.21).
The result demonstrated the less frequent pattern of co-mutational burden, potentially influencing the enhanced OS in NPM1+ AML patients and the diminished OS in NPM1– AML patients.
Source: https://clml-soho2023.elsevierdigitaledition.com/312/index.html
Clinical Trial: https://clinicaltrials.gov/study/NCT01688011
Maciejewski J, Pollyea D, Roboz G, Seiter K, Scott B, DeGutis I, Kiselev P, Yu E, McBride A, Heydendael W, Erba H. Prognostic Effect of Co-Mutations on Patients With NPM1+ Acute Myeloid Leukemia (AML) Enrolled in the Connect® Myeloid Registry.
