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Profile Name FLT3 act mut
Gene Variant Detail

FLT3 act mut (gain of function)

Relevant Treatment Approaches FLT3 Inhibitor

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Molecular Profile Indication/Tumor Type Response Type Relevant Treatment Approaches Therapy Name Approval Status Evidence Type Efficacy Evidence References
FLT3 act mut acute myeloid leukemia sensitive FLT3 Inhibitor Cytarabine + Daunorubicin + Sunitinib Phase Ib/II Actionable In a Phase Ib/II trial, 59% (13/22) of acute myeloid leukemia patients harboring FLT3 activating mutations achieved complete remission following treatment with Sutent (sunitinib) in combination with Cytarabine and Daunorubicin (PMID: 25818407). 25818407
FLT3 act mut leukemia sensitive FLT3 Inhibitor Pexidartinib Preclinical - Cell line xenograft Actionable In a preclinical study, PLX3397 inhibited FLT3 autophosphorylation in leukemia cells overexpressing FLT3 or harboring FLT3 activating mutations, and inhibited growth of leukemia cells harboring FLT3-ITD mutations in culture and in cell line xenograft models (ASH Annual Meeting Abstracts 2011 118: 3632). detail...
FLT3 act mut acute myeloid leukemia sensitive FLT3 Inhibitor Crenolanib Phase II Actionable In a Phase II trial, relapsed or refractory acute myeloid leukemia patients harboring FLT3 activating mutations without a history of FLT3 therapy demonstrated a significantly greater overall survival and event free survival compared to those that had prior FLT3 therapy when treated with Crenolanib (ASH meeting, Dec 2014, abstract #389). detail...
FLT3 act mut acute myeloid leukemia sensitive Palbociclib Preclinical Actionable In a preclinical study, Ibrance (palbociclib) blocked growth, induced apoptosis, and inhibited STAT activation in human FLT3-ITD positive human acute myeloid leukemia cells in culture (PMID: 27099147). 27099147
FLT3 act mut acute myeloid leukemia sensitive FLT3 Inhibitor Palbociclib + TCS 359 Preclinical Actionable In a preclinical study, Ibrance (palbociclib) following TCS-359 treatment enhanced growth inhibition of FLT3-ITD positive acute myeloid leukemia cell lines in culture (PMID: 27099147). 27099147
FLT3 act mut acute myeloid leukemia sensitive FLT3 Inhibitor TCS 359 Preclinical Actionable In a preclinical study, TCS-359 inhibited growth of FLT3-ITD positive acute myeloid leukemia cell lines in culture (PMID: 27099147). 27099147
FLT3 act mut acute myeloid leukemia sensitive FLT3 Inhibitor Palbociclib + Quizartinib Preclinical Actionable In a preclinical study, Ibrance (palbociclib) and Vanflyta (quizartinib) were synergistic towards growth inhibition of FLT3-ITD positive acute myeloid leukemia cell lines in culture (PMID: 27099147). 27099147
FLT3 act mut acute myeloid leukemia sensitive FLT3 Inhibitor Palbociclib + Tandutinib Preclinical Actionable In a preclinical study, Ibrance (palbociclib) and tandutinib (MLN518) were synergistic towards growth inhibition of FLT3-ITD positive acute myeloid leukemia cell lines in culture (PMID: 27099147). 27099147
FLT3 act mut acute myeloid leukemia sensitive Palbociclib + SGI-1776 Preclinical Actionable In a preclinical study, Ibrance (palbociclib) and SGI-1776 were synergistic towards growth inhibition of FLT3-ITD positive acute myeloid leukemia cell lines in culture (PMID: 27099147). 27099147
FLT3 act mut acute myeloid leukemia sensitive VS-5584 Preclinical - Cell line xenograft Actionable In a preclinical study, VS-5584 inhibited PI3K/mTOR signaling and cell proliferation in a FLT3-ITD positive human acute myeloid leukemia cell line in culture, and inhibited tumor growth in xenograft models (PMID: 23270925). 23270925
FLT3 act mut acute myeloid leukemia predicted - sensitive Azacitidine + Glasdegib Case Reports/Case Series Emerging In a Phase Ib trial, the combination of Daurismo (glasdegib) and Vidaza (azacitidine) resulted in an improved overall survival in acute myeloid leukemia patients harboring FLT3 mutations compared to those with wild-type FLT3 (P=0.039) (PMID: 35488900; NCT02367456). 35488900
FLT3 act mut acute myeloid leukemia sensitive FLT3 Inhibitor Gilteritinib + Venetoclax Phase I Actionable In a Phase Ib trial, combination treatment with Venclexta (venetoclax) and Xospata (gilteritinib) demonstrated clinical activity in patients with acute myeloid leukemia harboring FLT3 internal tandem duplication or tyrosine kinase domain mutations, leading to a a modified composite complete response (mCRc) rate of 75% (42/56), duration of response of 4.9 mo., and median overall survival of 10 mo., with a mCRc rate of 56% (5/9) in patients with tyrosine kinase domain mutations (PMID: 35849791; NCT03625505). 35849791
FLT3 act mut acute myeloid leukemia predicted - sensitive FLT3 Inhibitor NMS-P088 Phase I Actionable In a Phase I trial, NMS-P088 demonstrated manageable safety and preliminary efficacy with responses in 5 of 12 patients with acute myeloid leukemia harboring FLT3 mutations (Cancer Res (2023) 83 (8_Supplement): CT025; NCT03922100). detail...
FLT3 act mut acute myeloid leukemia predicted - sensitive FLT3 Inhibitor BMF-500 Preclinical Actionable In a preclinical study, BMF-500 inhibited Flt3 phosphorylation and downstream signaling and decreased viability of acute myeloid leukemia cell lines harboring FLT3 activating mutations in culture and induced tumor regression and improved survival in xenograft models (Blood (2022) 140 (Supplement 1): 6191-6192). detail...