Midostaurin in patients with acute myeloid leukemia and FLT3-TKD mutations: A subanalysis from the RATIFY trial Journal Article
| Authors: | 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.; Döhner, K.; Stone, R. M.; Döhner, H.; Bloomfield, C. D.; Lo-Coco, F. |
| Article 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. © 2020 by The American Society of Hematology |
| Keywords: | adult; controlled study; event free survival; middle aged; gene mutation; major clinical study; overall survival; pathogenesis; placebo; disease free survival; follow up; gene; multiple cycle treatment; cohort analysis; genotype; hematopoietic stem cell transplantation; antineoplastic activity; protein tyrosine kinase; cancer regression; gene rearrangement; allogeneic hematopoietic stem cell transplantation; core binding factor; cd135 antigen; nucleophosmin; midostaurin; acute myeloid leukemia; npm1 gene; human; male; female; priority journal; article; flt3 tkd gene |
| Journal Title: | Blood Advances |
| Volume: | 4 |
| Issue: | 19 |
| ISSN: | 2473-9529 |
| Publisher: | American Society of Hematology |
| Date Published: | 2020-10-13 |
| Start Page: | 4945 |
| End Page: | 4954 |
| Language: | English |
| DOI: | 10.1182/bloodadvances.2020002904 |
| PUBMED: | 33049054 |
| PROVIDER: | scopus |
| PMCID: | PMC7556122 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 December 2020 -- Source: Scopus |
