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Association details:
| Biomarker: | FLT3-ITD mutation |
|---|---|
| Cancer: | Acute Myelogenous Leukemia |
| Drug: | Iclusig (ponatinib) (Multi-tyrosine kinase inhibitor) |
| Direction: | Sensitive |
Evidence:
Source:
Title:
Ponatinib for FLT3-ITD Acute Myelogenous Leukemia
Excerpt:
...Intermediate risk karyotype with FLT3-ITD activating mutant detected at diagnosis (mutant FLT3/wild-type allelic ratio higher than 10%) (appendix 16) 6....
Trial ID:
Source:
Title:
A PHASE-IB/II CLINICAL EVALUATION OF PONATINIB IN COMBINATION WITH AZACITIDINE IN FLT3-ITD POSITIVE ACUTE MYELOID LEUKAEMIA (ALLG AML M21)
Published date:
06/12/2020
Excerpt:
...to establish a recommended phase-II dose of azacitidine combined with ponatinib in pts with FLT3-ITD+ AML. Median OS for the entire population was 4.6 months. Responses were seen in 2 of 4 pts with post-allograft relapse, with one achieving CR.
Secondary therapy:
azacitidine
Source:
Title:
Efficacy and Synergy of Small Molecule Inhibitors Targeting FLT3-ITD+ Acute Myeloid Leukemia
Published date:
12/08/2021
Excerpt:
FLT3-ITD+ AML lines were extremely sensitive to ponatinib, cabozantinib and WS6 (IC50 < 4 nM). Respectively, these compounds displayed limited activity targeting FLT3-wt cell lines (IC50 > 200 nM).
DOI:
https:// doi.org/10.3390/cancers13246181
Source:
Title:
Activity of ponatinib against clinically-relevant AC220-resistant kinase domain mutants of FLT3-ITD
Excerpt:
Substitution of the FLT3 “gatekeeper” phenylalanine with leucine (F691L) conferred mild resistance to ponatinib, but substitutions at the FLT3 activation loop (AL) residue D835 conferred a high degree of resistance. Saturation mutagenesis of FLT3-ITD exclusively identified FLT3 AL mutations at positions D835, D839, and Y842.
DOI:
10.1182%2Fblood-2012-07-442871
Source:
Title:
Potent Activity of Ponatinib (AP24534) in Models of FLT3-Driven Acute Myeloid Leukemia and Other Hematologic Malignancies
Excerpt:
... data suggest that inhibition of FLT3-ITD by ponatinib inhibits MV4-11 cell viability through the induction of apoptosis….To examine the effect of ponatinib on FLT3-ITD–driven tumor growth in vivo, ponatinib (1–25 mg/kg), or vehicle, was administered orally, once daily for 28 days, to mice bearing MV4-11 xenografts. As shown in Fig. 4A, ponatinib potently inhibited tumor growth in a dose-dependent manner. Administration of 1 mg/kg, the lowest dose tested, led to significant inhibition of tumor growth (TGI = 46%, P < 0.01) and doses of 2.5 mg/kg or greater resulted in tumor regression.
DOI:
10.1158/1535-7163.MCT-10-1044
