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Association details:
| Biomarker: | FLT3-ITD mutation + FLT3 D835 |
|---|---|
| Cancer: | Acute Myelogenous Leukemia |
| Drug: | Xospata (gilteritinib) (Multi-tyrosine kinase inhibitor) |
| Direction: | Sensitive |
Evidence:
Source:
Title:
Gilteritinib Remains Clinically Active in Relapsed/Refractory FLT3 Mutated AML Previously Treated with FLT3 inhibitors
Published date:
11/04/2020
Excerpt:
...received gilteritinib for treatment of R/R FLT3mut+ AML...patients with both FLT3-ITD and FLT3-D835 mutation had similar response and survival to FLT3-ITD alone.
Source:
Title:
RAS MUTATIONS ARE THE DOMINANT MECHANISM OF SECONDARY RESISTANCE TO GILTERITINIB THERAPY FOR RELAPSED/REFRACTORY FLT3-MUTATED AML
Published date:
05/17/2018
Excerpt:
CONTRADICTING EVIDENCE: Adults with R/R FLT3-mutated AML...At study enrollment 26/29 (89.7%) had a FLT3-ITD mutation, including 5 (17.2%) with both FLT3-ITD and FLT3-D835 mutations. Three subjects (10.3%) had a FLT3-D835 mutation only. 23/29 progressed during gilteritinib therapy, 5 were withdrawn for transplant or toxicity, and one remains on gilteritinib in remission.
Trial ID:
Source:
Title:
Inhibition of BCL2A1 by STAT5 inactivation overcomes resistance to targeted therapies of FLT3-ITD/D835 mutant AML
Published date:
02/01/2022
Excerpt:
However, a type I TKI, gilteritinib, inhibited the expression of BCL2A1 through inactivation of STAT5 and alleviated TKI resistance of FLT3-ITD/D835. The combination of gilteritinib and venetoclax showed synergistic effects in the FLT3-ITD/D835 positive AML cells. The promoter region of BCL2A1 contains a BRD4 binding site. Thus, the blockade of BRD4 with a BET inhibitor (CPI-0610) downregulated BCL2A1 in FLT3-mutated AML cells and extended profound suppression of FLT3-ITD/D835 mutant cells. Therefore, we propose that BCL2A1 has the potential to be a novel therapeutic target in treating FLT3-ITD/D835 mutated AML.
DOI:
10.1016/j.tranon.2022.101354
