Midostaurin in patients with acute myeloid leukemia and FLT3-TKD mutations: A subanalysis from the RATIFY trial

Maria Teresa Voso*, Richard A. Larson, Dan Jones, Guido Marcucci, Thomas Prior, Jürgen Krauter, Michael Heuser, Serena Lavorgna, Josep Nomdedeu, Susan M. Geyer, Alison Walker, Andrew H. Wei, Jorge Sierra, Miguel A. Sanz, Joseph M. Brandwein, Theo M. de Witte, Joop H. Jansen, Dietger Niederwieser, Frederick R. Appelbaum, Bruno C. MedeirosMartin S. Tallman, Richard F. Schlenk, Arnold Ganser, Sergio Amadori, Yuan Cheng, Yin Miao Chen, Celine Pallaud, Ling Du, Alfonso Piciocchi, Gerhard Ehninger, John Byrd, Christian Thiede, Konstanze Döhner, Richard M. Stone, Hartmut Döhner, Clara D. Bloomfield, Francesco Lo-Coco

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

40 Scopus citations


The results from the RATIFY trial (ClinicalTrials.gov: NCT00651261; CALGB 10603) showed that midostaurin combined with standard chemotherapy significantly improved outcomes in patients with FMS-like tyrosine kinase 3 (FLT3)-mutated acute myeloid leukemia (AML), compared with placebo. In this post hoc subgroup analysis from the trial, we evaluated the impact of midostaurin in 163 patients with FLT3-tyrosine kinase domain (TKD) mutations. At a median follow-up of 60.7 months (95% CI, 55.0-70.8), the 5-year event-free survival (EFS) rate was significantly higher in patients treated with midostaurin than in those treated with placebo (45.2% vs 30.1%; P 5.044). A trend toward improved disease-free survival was also observed with midostaurin (67.3% vs 53.4%; P 5.089), whereas overall survival (OS) was similar in the 2 groups. Patients with AML and NPM1mut/FLT3-TKDmut or core binding factor (CBF)-rearranged/FLT3-TKDmut genotypes had significantly prolonged OS with or without censoring at hematopoietic cell transplantation (HCT), compared with NPM1WT/CBF-negative AMLs. The multivariable model for OS and EFS adjusted for allogeneic HCT in first complete remission as a time-dependent covariable, revealed NPM1 mutations and CBF rearrangements as significant favorable factors. These data show that NPM1 mutations or CBF rearrangements identify favorable prognostic groups in patients with FLT3-TKD AMLs, independent of other factors, also in the context of midostaurin treatment.

Original languageEnglish (US)
Pages (from-to)4945-4954
Number of pages10
JournalBlood Advances
Issue number19
StatePublished - Oct 2020

ASJC Scopus subject areas

  • Hematology


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