Dr Abaza on Addressing the Need for Additional Targeted Therapies in AML/MDS

"In both fields…we do need to develop agents that are biomarker specific and try to target high-risk patient populations. If we can have agents that attack splicing factor mutations and have efficacy against a subgroup of AML/MDS, that would be a win for the field, but we’re still far away from that."

Yasmin Abaza, MD, assistant professor of medicine (hematology and oncology) at the Feinberg School of Medicine at the Robert H. Lurie Comprehensive Cancer Center of Northwestern University, discusses unmet needs for patients with acute myeloid leukemia (AML) and high-risk myelodysplastic syndrome (MDS), as well as the ongoing evaluation of the investigational agent emavusertib (CA-4948) in the phase 1/2 TakeAim Leukemia trial (NCT04278768).

In both AML and MDS, there is an ongoing demand for targeted agents, particularly those with biomarker-specific activity that could address unmet needs in high-risk patient populations, Abaza begins. Splicing factor mutations are recognized as high-risk genetic alterations in these diseases, and the development of targeted therapies against this disease subset could represent a meaningful advancement in treatment, she notes. However, achieving this goal remains a challenge, and further clinical investigation is necessary to determine the efficacy of novel agents in this setting, Abaza explains.

The TakeAim Leukemia trial aims to address the critical need for additional targeted therapies in these malignancies by evaluating the small molecule kinase inhibitor emavusertib, Abaza states. Additionally, other kinase inhibitors, including IRAK and CLK inhibitors, are being explored to target similar mutational profiles, Abaza continues. The potential benefit of these agents remains to be determined, as current data are derived from a limited number of treated patients, according to Abaza. Larger studies are required to establish a clear efficacy signal and to assess whether these investigational therapies can provide a meaningful clinical benefit in AML and MDS, Abaza reiterates. Future results from TakeAim Leukemia will be critical in evaluating the role of this multitargeted approach within the evolving treatment paradigm, she concludes.