Effect of NPM1 Mutation Subtype and Co-Mutation Patterns on the Outcomes of Acute Myeloid Leukemia.
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INTRODUCTION: NPM1 mutated AML without FLT3-ITD is considered "favorable" per the recent ELN 2022 criteria. However, our center has been challenged with treatment-refractory patients, prompting a search for additional prognostic factors. METHODS: We reviewed records of NPM1 AML patients from 2015 to 2024. Factors associated with event-free survival (EFS) and overall survival (OS) were evaluated using Cox regression. RESULTS: Among 141 patients with NPM1 AML, subtype A was the most common (N = 99), followed by subtype D (N = 10), subtype B (N = 6), subtype G/I/J/K/R (N = 3/5/3/2/1) and other subtypes (N = 12). Ninety patients received chemotherapy (chemo), 41 received hypomethylating agent +/- venetoclax (HMA/ven) and 10 did not receive specific anti-AML therapy. At 12 months, EFS for subtypes A, D, B, G/I/J/K/R, and other subtypes were 49%, 58%, 50%, 49%, and 31%, and OS were 71%, 79%, 50%, 44%, and 56%, respectively. Fifty patients had allogeneic stem cell transplants: 33 in CR1 and 17 in CR2+. EFS at 12 months post-HSCT was 72%. On multivariable analysis, co-mutation with KRAS (HR: 2.69, 95% CI: 1.20-6.00) or TET2 (HR: 1.99, 95% CI: 1.22-3.26) was associated with worse EFS. For each 50 k/mm3 increase in WBC at diagnosis, the risk of relapse or death increased by 21%. For OS, co-mutation with IDH1/IDH2 (HR: 0.40, 95% CI: 0.21-0.74) was associated with better OS, whereas co-mutation with SRSF2 (HR: 2.70, 95% CI: 1.35-5.40) was associated with worse OS. CONCLUSION: We did not find a statistically significant difference in EFS and OS among the NPM1 subtypes. However, our results showed that the prognoses of NPM1 AML can be influenced by other co-occurring mutations. A larger study is needed to confirm our findings.