@article{3ec5bf95d9844462a4062567127fda1d,
title = "Midostaurin in patients with acute myeloid leukemia and FLT3-TKD mutations: A subanalysis from the RATIFY trial",
abstract = "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.",
author = "Voso, {Maria Teresa} and Larson, {Richard A.} and Dan Jones and Guido Marcucci and Thomas Prior and J{\"u}rgen Krauter and Michael Heuser and Serena Lavorgna and Josep Nomdedeu and Geyer, {Susan M.} and Alison Walker and Wei, {Andrew H.} and Jorge Sierra and Sanz, {Miguel A.} and Brandwein, {Joseph M.} and {de Witte}, {Theo M.} and Jansen, {Joop H.} and Dietger Niederwieser and Appelbaum, {Frederick R.} and Medeiros, {Bruno C.} and Tallman, {Martin S.} and Schlenk, {Richard F.} and Arnold Ganser and Sergio Amadori and Yuan Cheng and Chen, {Yin Miao} and Celine Pallaud and Ling Du and Alfonso Piciocchi and Gerhard Ehninger and John Byrd and Christian Thiede and Konstanze D{\"o}hner and Stone, {Richard M.} and Hartmut D{\"o}hner and Bloomfield, {Clara D.} and Francesco Lo-Coco",
note = "Funding Information: Conflict-of-interest disclosure: M.T.V. has received research funding and is a member of the Speakers Bureau for Celgene. R.A.L. has served on independent data safety monitoring committees and acted as a consultant or advisor and has received clinical research support from Novartis. D.J. has received clinical research support from Novartis. G.M. has acted as a consultant or advisor for trials supported by Novartis. J.K. has acted as a consultant or advisor for Amgen, Astellas, Bristol-Myers Squibb, Daiichi Sankyo, and Pfizer. M.H. has acted as a consultant or advisor for AbbVie, Daiichi Sankyo, Novartis, Pfizer, and Bayer Pharma and has received clinical research support from Pfizer, Daiichi Sankyo, Karyopharm, BerGenBio, Bayer Pharma, Novartis, and Astellas. J.N. has acted as consultant or advisor for Novartis. A.W. has received clinical research support from Novartis. A.H.W. has acted as a consultant or advisor for Novartis, Astellas, Pfizer, MacroGenics, AbbVie, Gen-entech, Servier, Celgene, Takeda, and Argenix; has consulted for Amgen, AstraZeneca, and Janssen; is a member of the speakers bureau for AbbVie/Genentech and Novartis; has received research funding from Novartis, Celgene, AbbVie, Servier, AstraZeneca, and Amgen; and is a former employee of the Walter and Eliza Hall Institute and receives a fraction of its royalty stream related to venetoclax. J.S. has acted as a consultant or advisor for Pfizer, Daiichi Sankyo, AbbVie, Novartis, Astellas, and Roche and is a member of the speakers{\textquoteright} bureau for Novartis, Pfizer, Daiichi Sankyo, and AbbVie. M.A.S. has acted as a consultant or advisor for Teva Pharmaceutical Industries, Daiichi Sankyo, Orsenix, AbbVie, Novartis, and Pfizer. J.M.B. has acted as a consultant or advisor for Novartis, Celgene, Pfizer, Astellas, Teva, and Roche and has received research funding from Celgene. T.M.d.W. has acted as a consultant or advisor for Novartis, Celgene, Johnson & Johnson, and Incyte and has received clinical research support from Novartis, Celgene, and Johnson & Johnson. D.N. reports support from Cel-lectis and Daiichi and has participated in a Novartis speakers{\textquoteright} bureau outside the scope of the submitted work. B.C.M. has acted as a consultant or advisor for Celgene, Novartis, and Astellas and is currently employed by Roche/Genentech. M.S.T. has acted as a consultant or advisor for AbbVie, BioLineRx, Daiichi Sankyo, Orsenix, KAHR Medical, Rigel Pharmaceuticals, Nohla, Delta Fly Pharma, Tetraphase, Oncolyze, and Jazz Pharmaceuticals; has received clinical research funding from AbbVie, Cellerant Therapeutics, Orsenix, ADC Therapeutics, and BioSight; and has received royalties from UpToDate. R.F.S. has acted as a consultant or advisor for Pfizer and Daiichi Sankyo; is a member of the speakers{\textquoteright} bureau for Novartis, Pfizer, and Daiichi Sankyo; and has received clinical research funding from Pfizer, Daiichi Sankyo, PharmaMar, AstraZeneca, and Roche. A.G. has received clinical research support from Novartis. S.A. has acted as a consultant or advisor for Novartis and Daiichi Sankyo. Y.C., Y.M.C., and L.D. disclose employment with Novartis Pharmaceuticals Corporation. C.D. discloses Funding Information: The authors acknowledge the support of the National Institutes of Health, National Cancer Institute grants U24 CA196171 and U10 CA180821 (Alliance for Clinical Trials in Oncology), UG1 CA233338 (C.D.B.), and U10 CA180867 (Dana-Farber Cancer Institute); AIRC 5x1000 call “Metastatic disease: the key unmet need in oncology to MYNERVA” project, #21267 (MYeloid NEoplasms Research Venture AIRC) (M.T.V.); the Deutsche Forschungs-gemeinschaft (SFB 1074, project B3) (K.D.); and Catalan and Spanish government grants (2017 SGR 1395 and PERIS SLT002/ 16/00433 and ISCIII FIS PI17/01246) (J.S.). Study CALGB (Alliance) 10603 was funded in part by Novartis (CALGB is now part of the Alliance for Clinical Trials in Oncology). Funding Information: The authors acknowledge the support of the National Institutes of Health, National Cancer Institute grants U24 CA196171 and U10 CA180821 (Alliance for Clinical Trials in Oncology), UG1 CA233338 (C.D.B.), and U10 CA180867 (Dana-Farber Cancer Institute); AIRC 5x1000 call ?Metastatic disease: the key unmet need in oncology to MYNERVA? project, #21267 (MYeloid NEoplasms Research Venture AIRC) (M.T.V.); the Deutsche Forschungsgemeinschaft (SFB 1074, project B3) (K.D.); and Catalan and Spanish government grants (2017 SGR 1395 and PERIS SLT002/ 16/00433 and ISCIII FIS PI17/01246) (J.S.). Study CALGB (Alliance) 10603 was funded in part by Novartis (CALGB is now part of the Alliance for Clinical Trials in Oncology). The authors regretfully acknowledge the passing of 2 of the senior authors (C.D.B. and F.L.-C.), who made immense contributions to the design and analysis of the study, and to the writing of the manuscript.",
year = "2020",
month = oct,
doi = "10.1182/BLOODADVANCES.2020002904",
language = "English (US)",
volume = "4",
pages = "4945--4954",
journal = "Blood advances",
issn = "2473-9529",
publisher = "American Society of Hematology",
number = "19",
}