FLT3 inhibitors in acute myeloid leukemia: ten frequently asked questions

Association of fludarabin, cytarabine, and fractioned gemtuzumab followed by hematopoietic stem cell transplantation for first‐line refractory acute myeloid leukemia in children: A single‐center experience

“…Gilteritinib, a selective FLT3 inhibitor, has also been recently approved in adult patients 17 . Other TKI, such as quizartinib and crenolanib, are currently being tested in children in ongoing phase I and II trials 18 . However, the best TKI for pediatric AML remains to be identified.…”

Clinical implications of recurrent gene mutations in acute myeloid leukemia

“…Targeting mutant FLT3 by small molecule inhibitors has rapidly emerged as a new therapeutic approach in patients with AML. Different FLT3 inhibitor therapeutic agents have been developed and are summarized in Tables 1, 2 [9,[37][38][39][40][41][42][43][44][45][46][47][48][49][50][51][52][53].…”

“…A new category of "myeloid neoplasms with germline predisposition" has been provided by the new WHO classification and adopted by 2017 ELN Recommendations [2]. [37] EFS and OS at 2 years were 39% and 34% in younger and 53% and 46% in older patients, respectively [38] Recommended as front line therapy for AML with FLT3-ITD and FLT3-TKD [9,39] Sunitinib Some promising results in phase I/II clinical trials, but with high incidence of adverse effects [40,41] Gilteritinib a R/R FLT3-mutated AML, median OS for single agent gilteritinib was significantly longer than chemotherapy (9.3 months vs. 5.6 months). Median EFS was 2.8 months in the gilteritinib group and 0.7 months in chemotherapy group [42] Recommended as new standard therapy for R/R FLT3-mutated AML [43] Lestaurtinib Failed to demonstrate any overall clinical benefit in a phase III trial when combined with intensive chemotherapy in patients with newly diagnosed FLT3-ITD-mutated AML [9,44,45] Crenolanib a Combine with 7 + 3 regimen can overcome the poor prognostic implication of adverse mutations co-occurring with mutated FLT3 [46] Incorporation of crenolanib into frontline intensive chemotherapy resulted high ORR and may replace Midostaurin in the upfront setting [47] Type 2 Quizartinib a Showed efficacy in multiple clinical trials in R/R AML with FLT3-ITD mutation [48][49][50] Recommended for patients with rapidly proliferative disease and very poor prognosis [51] Sorafenib Combine with intensive chemotherapy improves OS in newly diagnosed, FLT3-ITD mutated AML regardless allogeneic HSCT [52] Improved OS for FLT3-ITD AML relapsing after allo-HSCT […”

“…Other recurrent gene mutations have been reported in AML patients [3][4][5][6][7][8]. Furthermore, the important roles of recurrent gene mutation in AML pathogenesis had been explored and gene mutation-targeted therapies had been developed [8][9][10][11][12][13][14][15]. Certain genes have been proved to be specifically related to the leukemia pathogenesis, such as pre-leukemic cell identification, particularly in AML patients with mutated DNMT3A and TET2 [16,17].…”

Novel Approaches to Target Mutant FLT3 Leukaemia

“…Several small-molecule TKI targeting FLT3 have been developed and tested. (Recently reviewed in [ 105 , 106 ].) First-generation multi-kinase inhibitors (sorafenib, midostaurin, lestaurtinib) are characterized by a broad-spectrum of drug targets, whereas second generation inhibitors (quizartinib, crenolanib, gilteritinib) show more potent and specific FLT3 inhibition, and are thereby accompanied by less toxic effects.…”