A phase I/IIa trial observed that emavusertib downregulates pathways associated with heme metabolism, proliferation, and cell cycle regulation that could translate into improved outcomes for patients with relapsed or refractory acute myeloid lymphoma (AML) or higher-risk myelodysplastic syndromes (MDS).
The results were presented by Klaus Metzeler, MD, of the University Hospital Leipzig, and colleagues at the 2023 Society for Immunotherapy of Cancer Annual Meeting. “Here, we describe our insights from RNA sequencing (RNA-seq) applied to clinical samples from the ongoing TakeAim Leukemia trial,” wrote Metzeler and colleagues.
The multicenter, open-label TakeAim Leukemia trial (NCT04278768) treated patients with relapsed or refractory AML or higher-risk MDS with the oral IRAK4 inhibitor emavusertib. RNA-seq was performed on mononuclear cells from bone marrow or peripheral blood from 26 patients with AML and 16 patients with MDS, including 24 paired samples.
Researchers saw decreased gene expression levels of the NF-κB target genes IL1β and IER3 (P≤.05) in patients who responded to emavusertib compared with patients who didn’t.
“Previous clinical research supports our findings describing [these genes] as important markers in the prognosis of AML [and] MDS,” researchers wrote. “IL1β and IER3 are highly expressed in patients with AML and MDS and associated with poor prognosis.”
Researchers also noted that ongoing studies will attempt to identify treatment response biomarkers, while future research will “examine the correlations of gene expression with mutational profiles, splicing factor mutations, emavusertib dose regimens, and use of proteomics technologies to assess targeted kinase phosphorylation levels and quantification of soluble markers.”
Metzeler K, Platzbecker U, Winer E, et al. Transcriptome analyses in patients with myeloid malignances treated with the IRAK4 inhibitor emavusertib. Abstract #688. Presented at the 2023 Society for Immunotherapy of Cancer Annual Meeting; November 1-5, 2023; San Diego, California.