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Association details:
| Biomarker: | FLT3-ITD mutation + FLT3 D835Y |
|---|---|
| Cancer: | Acute Myelogenous Leukemia |
| Drug: | Vanflyta (quizartinib) (FLT3 inhibitor) + milademetan (RAIN-32) (MDM2 inhibitor) |
| Direction: | Sensitive |
Evidence:
Source:
Title:
COMBINATION OF FLT3 INHIBITOR QUIZARTINIB AND MDM2 INHIBITOR MILADEMETAN RESULTS IN GREATER PRE-CLINICAL ANTI-LEUKEMIC ACTIVITY IN FLT3-ITD MUTANT/P53 WILD-TYPE ACUTE MYELOID LEUKEMIA MODELS
Published date:
05/17/2018
Excerpt:
We further investigated the effect of the combination regimen by using quizartinib and murine specific MDM2 inhibitor DS-5272 in murine leukemia cell lines Ba/F3-FLT3-ITD, Ba/F3-FLT3-ITD+F691L and Ba/F3-FLT3-ITD+D835Y, which harbor FLT3 ITD, ITD plus F691L and ITD plus D835Y mutations, respectively....Combination indexes (CIs) were 0.25 ± 0.06, 0.61 ± 0.03, 0.62 ± 0.06, 0.29 ± 0.004 and 0.50 ± 0.03, respectively, in MV-4-11, MOLM-13, MOLM-14, Ba/F3-FLT3-ITD+F691L and D835Y cell lines. All these cell lines harbor FLT3 ITD or ITD plus TKD point mutations. The combination regimen triggered synergistic pro-apoptotic effect in a p53 dependent manner.
