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

被引：44

作者：

Voso, Maria Teresa ^{[1
]}

Larson, Richard A. ^{[2
]}

Jones, Dan ^{[3
]}

Marcucci, Guido ^{[3
]}

Prior, Thomas ^{[3
]}

Krauter, Jurgen ^{[4
,5
]}

Heuser, Michael ^{[4
]}

Lavorgna, Serena ^{[1
]}

Nomdedeu, Josep ^{[6
,7
]}

Geyer, Susan M. ^{[8
]}

Walker, Alison ^{[3
]}

Wei, Andrew H. ^{[9
,10
]}

Sierra, Jorge ^{[6
,7
]}

Sanz, Miguel A. ^{[11
,12
]}

Brandwein, Joseph M. ^{[13
]}

de Witte, Theo M. ^{[14
]}

Jansen, Joop H. ^{[14
]}

Niederwieser, Dietger ^{[15
]}

Appelbaum, Frederick R. ^{[16
]}

Medeiros, Bruno C. ^{[17
]}

Tallman, Martin S. ^{[18
]}

Schlenk, Richard F. ^{[19
,20
,21
]}

Ganser, Arnold ^{[4
]}

Amadori, Sergio ^{[1
]}

Cheng, Yuan ^{[22
]}

Chen, YinMiao ^{[22
]}

Pallaud, Celine ^{[23
]}

Du, Ling ^{[24
]}

Piciocchi, Alfonso ^{[25
]}

Ehninger, Gerhard ^{[26
]}

Byrd, John ^{[3
]}

Thiede, Christian ^{[26
]}

Dohner, Konstanze ^{[19
]}

Stone, Richard M. ^{[27
]}

Dohner, Hartmut ^{[19
]}

Bloomfield, Clara D. ^{[3
]}

Lo-Coco, Francesco ^{[1
]}

机构：

[1] Univ Tor Vergata, Dept Biomed & Prevent, Via Montpellier 1, I-00133 Rome, Italy

[2] Univ Chicago, Dept Med, Chicago, IL 60637 USA

[3] Ohio State Univ, Comprehens Canc Ctr, Columbus, OH USA

[4] Med Sch, Dept Hematol Hemostasis Oncol & Stem Cell Transpl, Hannover, Germany

[5] Klinikum Braunschweig, Dept Hematol & Oncol, Braunschweig, Germany

[6] Autonomous Univ Barcelona, Hematol Dept, Hosp Santa Creu & St Pau, Barcelona, Spain

[7] Autonomous Univ Barcelona, Jose Carreras Leukemia Res Inst, Barcelona, Spain

[8] Mayo Clin, Alliance Stat & Data Ctr, Rochester, NY USA

[9] Alfred Hosp, Dept Clin Hematol, Melbourne, Vic, Australia

[10] Monash Univ, Melbourne, Vic, Australia

[11] Univ Valencia, Hosp Univ & Politecn La Fe, Dept Hematol, Valencia, Spain

[12] Inst Carlos III, Ctr Invest Biomed Red Canc, Madrid, Spain

[13] Univ Alberta, Dept Med, Edmonton, AB, Canada

[14] Radboud Univ Nijmegen, Nijmegen Ctr Life Sci, Dept Tumor Immunol, Med Ctr, Nijmegen, Netherlands

[15] Univ Leipzig, Dept Hematol, Leipzig, Germany

[16] Fred Hutchinson Canc Res Ctr, Clin Res Div, Seattle, WA USA

[17] Stanford Univ, Div Hematol, Stanford Comprehens Canc Ctr, Stanford, CA USA

[18] Mem Sloan Kettering Canc Ctr, Div Hematol Malignancies, Leukemia Serv, New York, NY USA

[19] Univ Hosp Ulm, Dept Internal Med III, Ulm, Germany

[20] Heidelberg Univ Hosp, Dept Internal Med 5, Heidelberg, Germany

[21] German Canc Res Ctr, NCT Trial Ctr, Heidelberg, Germany

[22] Novartis Pharmaceut, E Hanover, NJ USA

[23] Novaremed AG, Basel, Switzerland

[24] Novartis Pharmaceut, Cambridge, MA USA

[25] GIMEMA Data Ctr, Rome, Italy

[26] Tech Univ Dresden, Univ Klinikum Carl Gustav Carus, Med Klin & Poliklin 1, Dresden, Germany

[27] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA USA

来源：

BLOOD ADVANCES | 2020年 / 4卷 / 19期

基金：

美国国家卫生研究院;

关键词：

MINIMAL RESIDUAL DISEASE; INTERNAL TANDEM DUPLICATION; ACUTE MYELOGENOUS LEUKEMIA; KINASE DOMAIN MUTATIONS; PROGNOSTIC-SIGNIFICANCE; CAPILLARY-ELECTROPHORESIS; YOUNGER ADULTS; NPM1; MUTATIONS; AML; CHEMOTHERAPY;

D O I：

10.1182/bloodadvances.2020002904

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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=.044). A trend toward improved disease-free survival was also observed with midostaurin (67.3% vs 53.4%; P=.089), whereas overall survival (OS) was similar in the 2 groups. Patients with AML and NPM1(mut)/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 NPM1(WT)/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.

引用

页码：4945 / 4954

页数：10

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