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Gene | FLT3 |
Variant | act mut |
Impact List | unknown |
Protein Effect | gain of function |
Gene Variant Descriptions | FLT3 act mut indicates that this variant results in a gain of function in the Flt3 protein. However, the specific amino acid change has not been identified. |
Associated Drug Resistance | |
Category Variants Paths |
FLT3 mutant FLT3 act mut |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
FLT3 act mut | acute myeloid leukemia | sensitive | 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 | leukemia | sensitive | 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 | 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 | sensitive | 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 | 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 | acute myeloid leukemia | sensitive | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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... |