New genetic test reclassifies half of AML patients, reshaping treatment strategy
Researchers have developed a genetic classification system that reorganizes how doctors assess risk in a common form of blood cancer, potentially sparing thousands of patients from unnecessary aggressive treatment. The test could reshape treatment protocols and clinical trial design across oncology centers worldwide.
Originaltitel: Unravelling co-mutational patterns with prognostic implications in NPM1 mutated adult acute myeloid leukemia - a HARMONY study
<p><em>NPM1</em>-mutated (<em>NPM1</em>-mut) acute myeloid leukemia (AML) is generally associated with a more favorable outcome, although the presence of additional gene mutations can influence patient prognosis. We analyzed intensively-treated adult <em>NPM1</em>-mut AML patients included in the HARMONY Alliance database. A newly developed risk classification, which included combinations of co-mutations in <em>FLT3</em>-ITD, <em>DNMT3A</em>, <em>IDH1/IDH2</em>, and <em>TET2</em> genes, was applied to a training cohort of <em>NPM1</em>-mut AML patients included in clinical trials (n = 1001), an internal validation cohort more representative of real-world settings (n = 762), and an external validation cohort enrolled in UK-NCRI trials (n = 585). The HARMONY classification considered 51.8% of the <em>NPM1</em>-mut AML training cohort patients as favorable, 24.8% as intermediate, and 23.4% as adverse risk, with median overall survival (OS) of 14.4, 2.2, and 0.9 years, respectively; p < 0.001), thereby reclassifying 42.7% of NPM1-mut patients into a different European LeukemiaNet (ELN) 2022 risk category. These results were confirmed both in an internal and external validation cohort. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) in first complete remission (CR1) showed the highest benefit in the <em>NPM1</em>-mut adverse-risk subgroup. The HARMONY classification provides the basis for a refined genetic risk stratification for adult <em>NPM1</em>-mut AML with potential clinical impact on allo-HSCT decision-making.</p>