Internal tandem duplication (ITD) of the fms-related tyrosine kinase-3 gene ( FLT3) confer a poor prognosis in adult AML. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. Unfortunately, in our study, information on the site of insertion was not available in the whole cohort, and few patients harbored a TKD1 insertion.We did not carry out a statistical analysis of the insertion site given the heterogeneity in the treatment of patients analyzed and the small number of patients with an ITD inserted in the TKD1 domain. (A) Overall survival. J. Med. The first-generation FLT3is lack specificity for FLT3 and inhibit multiple downstream RTKs that may result in more off-target toxicities. In the R/R setting, the CRc rate was 64% (n=18/28) with a median OS of 12.0 months, with responses observed even in prior FLT3i exposed patients48. ABSTRACT. Musa Yilmaz, M. et al. evaluated the impact of AR in 323 patients with newly diagnosed FLT3-ITDmut AML. Clinical outcomes in patients with relapsed/refractory acute myeloid leukemia treated with gilteritinib who received prior midostaurin or sorafenib. Precision Medicine in Myeloid Malignancies: Hype or Hope? Canc. Our study has several limitations: (1) Our patients were selected from an observational registry, which can be interpreted as a limitation given the heterogeneity of treatments or as a strength because our data are thereby more similar to those observed in real-life clinical practice than those derived from a clinical trial26,27. Google Scholar, MM Patnaik 2018 The importance of FLT3 mutational analysis in acute myeloid leukemia Leuk. The authors declare no competing interests. Prognostic impact analyses of FLT3-ITD length were performed among patients treated with upfront IC regimens. J. Clin. 5 96 102, C Sargas 2020 Networking for advanced molecular diagnosis in acute myeloid leukemia patients is possible: The PETHEMA NGS-AML project Haematologica https://doi.org/10.3324/haematol.2020.263806, Article Rosnet, O. et al. evaluated the outcomes of sequential FLT3i-based therapies in FLT3mut AML. 13 95 100. These observations have made FLT3 an attractive drug target. 2). To mitigate prolonged myelosuppression with the triplet and avoid over-treatment, we perform an early bone marrow assessment on Cycle 1 Day 14 (Fig. Cite this article. Hematol. In the randomized phase III RATIFY trial of midostaurin combined with cytarabine and daunorubicin (3+7) induction and consolidation, midostaurin improved OS compared to placebo in patients <60years of age with newly diagnosed FLT3 (ITD and/or TKD) AML24, regardless of AR (0.7 or 0.7) or the type of mutation (ITD or TKD). Inhibition of mutant FLT3 receptors in leukemia cells by the small molecule tyrosine kinase inhibitor PKC412. Xuan, L. et al. PubMed and JM.A. Dipsit Digital de la Universitat de Barcelona: Prognostic impact of Informed consent was a requisite for patients alive at the time of data lock (January 2019). 2, 125 (2020). As we have already explained, our main goal was to validate two previous recurrently applied cutoffs: 39bp and 70bp. 1A). and P.M.; Data curation, J.M.A. Accumulating evidence have shown improved outcomes in FLT3-ITDmut patients receiving induction with higher dose anthracyclines57, cladribine58, or fludarabine added to induction backbone21, and incorporating FLT3i with induction (either first or second generation) in FLT3mut AML24,44,59,60 (Fig. Clin. Some studies showed a reduced CR rate, while others analyzing the IS in the same region found differences in OS. CAS A subsequent randomized phase IIb trial evaluated lower doses, 30 or 60mg of quizartinib daily, in patients with R/R FLT3-ITDmut AML. In the frontline setting, there was a sequential decrease in CRc rates (77%31%25%) and OS (16.76.01.4 months). Mali, R. S. et al. Prognostic Value of FLT3-Internal Tandem Duplication Residual Disease