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. 2025 Jun 30;2(4):100133.
doi: 10.1016/j.bneo.2025.100133. eCollection 2025 Nov.

Intensive chemotherapy vs venetoclax/hypomethylating agents for patients aged 60 to 75 years with favorable, NPM1-mutated AML

Andrew D Zale  1 , Venkata Preetam Sandeep Kaduluri  1 , Jonathan A Webster  1 , Mark J Levis  1 , Ivana Gojo  1 , Amy E DeZern  1 , Gabriel Ghiaur  1 , Lukasz P Gondek  1 , William Brian Dalton  1 , Theodoros Karantanos  1 , Tania Jain  1 , Gabrielle T Prince  1 , Richard J Jones  1 , B Douglas Smith  1 , Alexander J Ambinder  1
Affiliations

Intensive chemotherapy vs venetoclax/hypomethylating agents for patients aged 60 to 75 years with favorable, NPM1-mutated AML

Andrew D Zale et al. Blood Neoplasia. .

Abstract

Patients with nucleophosmin 1 (NPM1)-mutated acute myeloid leukemia (AML) without a FLT3-internal tandem duplication mutation are considered to have favorable-risk disease that may be cured with intensive chemotherapy (7+3; IC) alone. As patients age, the potential for cure without transplant is counterbalanced by morbidity associated with IC. Venetoclax combined with a hypomethylating agent (VEN/HMA) is approved for patients aged ≥75 years or those ineligible for IC, and the regimen is therefore frequently utilized in patients between 60 and 75 years of age. The differences in outcomes between patients with NPM1-mutated, favorable-risk AML who receive IC and VEN/HMA are unknown. We performed a retrospective analysis of patients aged 60 to 75 years with favorable risk, NPM1-mutated AML and compared overall survival (OS) between those treated with IC vs VEN/HMA. We identified 55 patients who met eligibility criteria. Thirty-six patients (65%) received first-line IC, and 19 patients (35%) received first-line VEN/HMA. There was no statistical difference in OS between groups (median survival: IC, 6.2 years; 95% CI, 3.26 years-NR, and VEN/HMA, 4.9 years; 95% CI, 1.1 years-NR). Sixty-day survival in the IC and VEN/HMA cohorts were 97.2% and 100%, respectively. In a univariate analysis, allogeneic hematopoietic cell transplant (alloHCT) in first remission was associated with improved OS (hazard ratio, 0.30; 95% CI, 0.12-0.74), although there were no differences when induction therapy was stratified by alloHCT status. These data suggest that outcomes for patients aged 60 to 75 years with NPM1-mutated AML are comparable between patients initially treated with IC or VEN/HMA.

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Conflict of interest statement

Conflict-of-interest disclosure: J.W. received funding from Amgen, Consumer Value Store, Servier, and Syndax. M.L. reports consultancy/honoraria from Astellas, Daiichi-Sankyo, Novartis, Syndax, GlaxoSmithKline, and Takeda. I.G. reports research funding from Incyte, Amgen, Merck, and Kura Oncology; and served on the advisory boards of In8Bio, Syndax, and Astellas. A.D. received funding from Bristol Myers Squibb, Novartis, Takeda, Pfizer, Agios, Keros, Geron, Astellas, Shattuck Labs, Kura, AbbVie, and Servier. T.J. receives institutional research support from Cell Therapeutic, Inc. Biopharma, Kartos Therapeutics Inc, Incyte, Bristol Myers Squibb, TScan Therapeutics, and Karyopharm Therapeutics; and reports advisory board participation with Bristol Myers Squibb, Incyte, AbbVie, CTI, Kite, Cogent Biosciences, Blueprint Medicine, Telios pharma, Protagonist Therapeutics, Galapagos, TScan Therapeutics, Karyopharm, MorphoSys, and In8Bio. B.D.S. reports consultancy for Servier. A.A. recieved funding from Astellas. The remaining authors declare no competing financial interests.

Figures

None
Graphical abstract
Figure 1.
Figure 1.
Study flowchart.
Figure 2.
Figure 2.
Outcomes of patients with favorable-risk, NPM1m AML by induction treatment regimen and alloHCT status. (A) Comparison of OS by induction treatment regimen. (B) Comparison of OS by induction treatment regimen in patients who underwent alloHCT. (C) Comparison of OS by induction treatment regimen in patients who did not undergo alloHCT. (D) Competing events analysis of NRM and relapse after alloHCT stratified by induction chemotherapy regimen. BMT, bone marrow transplant; NPM1m, NPM1-mutated.
See this image and copyright information in PMC

References

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