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

• DOI: 10.1182/bloodadvances.2020002904
• Publication Date: 2020-10-13T19:57:29Z
• Authors: 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. Appe...; Bruno C. Medeiros; Martin S. Tallman; Richard F. Schlenk; Arnold Ganser; Sergio Amadori; Yuan Cheng; YinMiao 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
• Keywords: Midostaurin; NPM1

Abstract The results from the RATIFY trial (ClinicalTrials.gov: NCT00651261; CALGB 10603) showed that midostaurin combined with standard chemotherapy significantly improved outcomes in patients FMS-like tyrosine kinase 3 (FLT3)–mutated acute myeloid leukemia (AML), compared placebo. In this post hoc subgroup analysis trial, we evaluated impact of 163 FLT3-tyrosine domain (TKD) mutations. At a median follow-up 60.7 months (95% CI, 55.0-70.8), 5-year event-free survival (EFS) rate was higher treated than those placebo (45.2% vs 30.1%; P = .044). A trend toward disease-free also observed (67.3% 53.4%; .089), whereas overall (OS) similar 2 groups. Patients AML and NPM1mut/FLT3-TKDmut or core binding factor (CBF)–rearranged/FLT3-TKDmut genotypes had prolonged OS without censoring at hematopoietic cell transplantation (HCT), NPM1WT/CBF-negative AMLs. multivariable model for EFS adjusted allogeneic HCT first complete remission as time-dependent covariable, revealed NPM1 mutations CBF rearrangements significant favorable factors. These data show identify prognostic groups FLT3-TKD AMLs, independent other factors, context treatment.