Publications by authors named "I Gathmann"
Article Synopsis
- The study investigates the genetic mutations in patients with FLT3-mutated acute myeloid leukemia (AML) who participated in a clinical trial comparing intensive chemotherapy with the drug midostaurin to a placebo.
- Sequencing of 475 patients revealed significant co-mutations, notably in NPM1, DNMT3A, and WT1, with NPM1 mutations found to improve the prognosis of patients with WT1 mutations.
- The research also highlights how specific mutations and treatment options impact patient outcomes, particularly showing that midostaurin may offer benefits for those with WT1 mutations.
In acute myeloid leukemia (AML) internal tandem duplications of the FLT3 gene (FLT3-ITD) are associated with poor prognosis. Retrospectively, we investigated the prognostic and predictive impact of FLT3-ITD insertion site (IS) in 452 patients randomized within the RATIFY trial, which evaluated midostaurin additionally to intensive chemotherapy. Next-generation sequencing identified 908 ITDs, with 643 IS in the juxtamembrane domain (JMD) and 265 IS in the tyrosine kinase domain-1 (TKD1).
View Article and Find Full Text PDFThe prospective randomized, placebo-controlled CALGB 10603/RATIFY trial (Alliance) demonstrated a statistically significant overall survival benefit from the addition of midostaurin to standard frontline chemotherapy in a genotypically-defined subgroup of 717 patients with FLT3-mutant acute myeloid leukemia (AML). The risk of death was reduced by 22% on the midostaurin-containing arm. In this post hoc analysis, we analyzed the cumulative incidence of relapse (CIR) on this study and also evaluated the impact of 12 4-week cycles of maintenance therapy.
View Article and Find Full Text PDFPatients with acute myeloid leukemia (AML) harboring FLT3 internal tandem duplications (ITDs) have poor outcomes, in particular AML with a high (≥0.5) mutant/wild-type allelic ratio (AR). The 2017 European LeukemiaNet (ELN) recommendations defined 4 distinct FLT3-ITD genotypes based on the ITD AR and the NPM1 mutational status.
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