EHA 2022: Targeted therapy emavusertib shows encouraging activity in MDS and AML with specific mutations

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Mutations in SF3B1 and U2AF1 can drive overexpression of activated IRAK4 — which regulates inflammation and promotes cancer cell growth and survival — and are associated with a poor prognosis for patients with high-risk myelodysplastic syndrome (HR-MDS) and acute myeloid leukaemia (AML).

Emavusertib is a targeted therapy that inhibits IRAK4 and FLT3, which also is frequently mutated in AML. Guillermo Garcia-Manero, M.D., led a Phase I/IIa study to investigate the safety and efficacy of emavusertib alone (Phase I) or in combination with either azacitidine or venetoclax (Phase IIa).

In 49 patients treated on the Phase I portion, emavusertib had manageable side effects and no Grade 4-5 treatment-related adverse events. In five AML and seven HR-MDS patients with SF3B1 or U2AF1 mutations, complete response (CR) rates were 40% and 57%, respectively.

Of three FLT3-mutant AML patients, one had a CR and two became negative for mutant FLT3. There were limited responses in patients without these mutations.

Early data for this ongoing trial suggest emavusertib is well-tolerated with encouraging activity, particularly for patients with select mutations.

Source: The University of Texas MD Anderson Cancer Center


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