Intensive induction chemotherapy vs hypomethylating agents in combination with venetoclax in NPM1-mutant AML Journal Article

   


Authors: Bewersdorf, J. P.; Shimony, S.; Shallis, R. M.; Liu, Y.; Berton, G.; Schaefer, E. J.; Zeidan, A. M.; Goldberg, A. D.; Stein, E. M.; Marcucci, G.; Bystrom, R. P.; Lindsley, R. C.; Chen, E. C.; Perez, J. R.; Stein, A.; Pullarkat, V.; Aldoss, I.; DeAngelo, D. J.; Neuberg, D. S.; Stone, R. M.; Garciaz, S.; Ball, B.; Stahl, M.
Article Title: Intensive induction chemotherapy vs hypomethylating agents in combination with venetoclax in NPM1-mutant AML
Abstract: Although intensive induction chemotherapy (IC) remains the standard of care for younger patients with acute myeloid leukemia (AML), hypomethylating agents + venetoclax (HMA/ VEN) can lead to durable remission among older patients with nucleophosmin 1 ( NPM1 ) mutations. Whether IC or HMA/VEN is superior in patients aged >= 60 years with NPM1-- mutant AML is unknown. We performed an international, multicenter retrospective cohort study of 221 patients (147 IC and 74 HMA/VEN) with previously untreated NPM1-mutant AML. Composite complete remission (cCR) (defined as CR + CR with incomplete count recovery) rate was similar for IC and HMA/VEN (cCR, 85% vs 74%; P = .067). Although overall survival (OS) was favorable with IC in unselected patients compared with HMA/VEN (24-month OS, 59% [95% confidence interval (CI), 52-69%] vs 38% [95% CI, 27-55%]; P = .013), it was not statistically different among patients aged 60-75 years (60% [95% CI, 52-70%] vs 44% [95% CI, 29-66%]; P = .069) and patients who received an allogeneic stem cell transplant (70% [95% CI, 58-85%] vs 66% [95% CI, 44-100%]; P = .56). Subgroup analyses suggested that patients with normal cytogenetics (24-month OS, 65% [95% CI, 56-74%] with IC vs 40% [95% CI, 26-60%] with HMA/VEN; P = .009) and without FLT3 internal tandem duplication mutations might benefit from IC compared with HMA/VEN (24-month OS, 68% [95% CI, 5979%] vs 43% [95% CI, 29-63%]; P = .008). In multivariable analysis, OS was not statistically different between patients treated with IC and HMA/VEN (hazard ratio for death with HMA/ VEN vs IC, 0.71; 95% CI, 0.40-1.27; P = .25).
Keywords: mutations; residual disease; acute myeloid-leukemia
Journal Title: Blood Advances
Volume: 8
Issue: 18
ISSN: 2473-9529
Publisher: American Society of Hematology  
Date Published: 2024-09-24
Start Page: 4845
End Page: 4855
Language: English
ACCESSION: WOS:001318311500001
DOI: 10.1182/bloodadvances.2024012858
PROVIDER: wos
PMCID: PMC11416634
PUBMED: 38941537
Notes: Article -- MSK Cancer Center Support Grant (P30 CA008748) acknowledged in PDF -- Source: Wos
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MSK Authors
  1. Eytan Moshe Stein
    342 Stein
  2. Aaron David Goldberg
    106 Goldberg
  3. Jan Philipp Bewersdorf
    96 Bewersdorf
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