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 (MDS) and acute myeloid leukemia (AML). Emavusertib is a targeted therapy that inhibits IRAK4 and FLT3, which also is frequently mutated in AML.
Guillermo Garcia-Manero, MD
Guillermo Garcia-Manero, MD, of the Department of Leukemia at The University of Texas MD Anderson Cancer Center, 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). Results were presented at the European Hematology Association (EHA) 2022 Congress (Abstract S129).
In 49 patients treated in the phase I portion, emavusertib had manageable side effects and produced no grade 4 or 5 treatment-related adverse events. In five patients with AML and seven with high-risk MDS with SF3B1 or U2AF1 mutations, complete response rates were 40% and 57%, respectively. Of three patients with FLT3-mutant AML, one had a complete response 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.
Disclosure: For full disclosures of the study authors, visit library.ehaweb.org.
