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Midostaurin in patients with acute myeloid leukemia and FLT3-TKD mutations: a subanalysis from the RATIFY trial. Blood advances Voso, M. T., Larson, R. A., Jones, D., Marcucci, G., Prior, T., Krauter, J., Heuser, M., Lavorgna, S., Nomdedeu, J., Geyer, S. M., Walker, A., Wei, A. H., Sierra, J., Sanz, M. A., Brandwein, J. M., de Witte, T. M., Jansen, J. H., Niederwieser, D., Appelbaum, F. R., Medeiros, B. C., Tallman, M. S., Schlenk, R. F., Ganser, A., Amadori, S., Cheng, Y., Chen, Y., Pallaud, C., Du, L., Piciocchi, A., Ehninger, G., Byrd, J., Thiede, C., Dohner, K., Stone, R. M., Dohner, H., Bloomfield, C. D., Lo-Coco, F. 2020; 4 (19): 4945–54

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 = .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 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.

View details for DOI 10.1182/bloodadvances.2020002904

View details for PubMedID 33049054