Clinical outcomes associated with
                    <i>NPM1</i>
                    mutations in newly diagnosed acute myeloid leukemia

doi:10.1002/cncr.70568

DOI: 10.1002/cncr.70568 ISSN: 0008-543X

Clinical outcomes associated with NPM1 mutations in newly diagnosed acute myeloid leukemia

Aziz Farhat, Georgina El Hajjar, Hagop Kantarjian, Koji Sasaki, Nicholas J. Short, Branko Cuglievan, Sanam Loghavi, Keyur Patel, Alex Bataller, Wei Ying Jen, Musa Yilmaz, Guillermo Montalban‐Bravo, Danielle Hammond, Naveen Pemmaraju, Naval Daver, Farhad Ravandi, Elias Jabbour, Tapan Kadia, Gautam Borthakur, Guillermo Garcia‐Manero, Courtney D. DiNardo, Ghayas C. Issa

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Abstract

Background

Nucleophosmin 1‐mutated ( NPM1mt ) acute myeloid leukemia (AML) is associated with a relatively favorable prognosis though long‐term outcomes remain suboptimal without clear predictors identified by therapy.

Methods

In a retrospective analysis, the authors identified 396 patients (18%) with newly diagnosed (ND) NPM1mt AML treated at The University of Texas MD Anderson Cancer Center and analyzed their outcomes. Using a Cox regression model, they analyzed predictors of survival in newly diagnosed NPM1mt AML across various therapies.

Results

Those treated with high intensity chemotherapy had a median overall survival (OS) of 84.7 months with a 5‐year rate of 53% (95% CI, 44%–61%) whereas those treated with a combination of a hypomethylating agent (HMA) and venetoclax had a median OS of 23.3 months with a 5‐year rate of 19% (95% CI, 5%–39%). The combination of cladribine, low‐dose cytarabine, and venetoclax alternating with azacitidine and venetoclax yielded better survival compared with HMA and venetoclax in an age‐matched analysis (5‐year OS rate of 74% vs. 24%) ( p = .048).

Conclusion

Among patients with NPM1mt treated with high‐intensity chemotherapy, older age, a poor performance status, and presence of a FLT3‐ITD mutation or extramedullary disease predicted a worse overall survival. For patients treated with a hypomethylating agent and venetoclax, older age was the only predictor of worse long‐term outcomes. These findings can be used for risk‐stratification of newly diagnosed NPM1mt AML and provide benchmarks of response and survival for this subtype.