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NPM1 Genotypes and Outcomes in AML


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In an AIEOP-BFM and COG-SWOG intergroup collaborative study reported in the Journal of Clinical Oncology, Tregnago et al found that patients with acute myeloid leukemia (AML) with NPM1 type D variants had significantly poorer event-free and overall survival vs those with non-D variants.

Study Details

The study included 348 pediatric and 75 adult patients with AML with known NPM1 variants, including 30 with NPM1-D variants and 393 non-D variants, as well as 2,287 patients with wild-type NPM1, with available outcome data from patients enrolled in pediatric or adult trials. NPM1 variants were correlated with event-free and overall survival.

Key Findings

For all adult and pediatric patients combined, those with NPM1-D had significantly poorer 5-year event fee survival (51%) compared with those with non-D variants (71%, P = .0449) and similar outcomes vs those with wild-type NBM1 (44%). Among patients with non-D variants, 5-year rates were 67% for A variants, 75% for B variants, 73% for A-like variants, and 80% for non–A-like variants.

For overall survival, patients with NBM1-D had significantly poorer 5-year rates (63%) compared with those with non-D variants (86%, P = .0053) and similar rates vs wild-type NPM1 (61%). Among patients with non-D variants, 5-year rates were 85% for A variants, 86% for B variants, 90% for A-like variants, and 88% for non–A-like variants.

On multivariate analysis, type D was found to be an independent prognostic factor for inferior event-free survival (hazard ratio [HR] = 2.00, P = .036) and overall survival (HR = 3.00, P = .005).

The investigators concluded: “The evaluation of specific NPM1 genotypes identified AML patients with type D mutations being significantly associated with inferior outcomes, suggesting a reclassification of D cases to higher-risk groups.”

Martina Pigazzi, PhD, of the University of Padova, Italy, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was supported by grants from Istituto di Ricerca Pediatrica-Fondazione Città della Speranza, Associazione Italiana Contro le Leucemielinfomi e Myeloma, and others. For full disclosures of the study authors, visit ascopubs.org.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
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