Dr Wang on Research With Menin Inhibitors in AML/ALL

Eunice Wang, MD, chief, Leukemia Service, Department of Medicine; medical director, Chemotherapy/Infusion Center; leader, leukemia clinical disease team; professor, oncology; assistant member, Tumor Immunology Program, Department of Immunology, Roswell Park Comprehensive Cancer Center, discusses updated data and ongoing research with menin inhibitors in patients with acute leukemias, as presented at the 2024 EHA Congress.

Menin inhibitors are emerging as a promising class of agents for targeting specific subsets of acute leukemia, and there was considerable excitement about this drug class at the meeting, Wang begins. Menin inhibitors are designed to target acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) characterized by KMT2A or MLL rearrangements, as well as NPM1 mutations, she details, adding that this novel approach could offer a targeted therapy option for patients previously underserved by conventional treatments.

Among the menin inhibitors in development, revumenib (SNDX-5613) has garnered significant attention, Wang says. Revumenib is a potent, oral, selective inhibitor of the menin-KMT2A interaction. Updated findings from the phase 2 AUGMENT-101 study (NCT04065399) were presented at the Congress, and demonstrated the safety and the efficacy of this compound across the entire subset of patients with KMT2A-rearranged acute leukemias, Wang reports. The study showed a complete response (CR) and CR with hematologic recovery (CRh) rate of 23% (95% CI, 12.7%-35.8%; P = .0036) among 57 evaluable patients. The FDA granted priority review to revumenib in KMT2A-rearranged acute leukemia in March 2024 and extended the Prescription Drug User Fee Act target action date for the new drug application seeking the agent’s approval to December 26, 2024. The AUGMENT-101 data supported the application seeking the FDA approval of revumenib for this patient population, Wang affirms.

Additionally, at the meeting, updates were provided on newer inhibitors and combination therapies, Wang continues. Notably, data from the phase 1/2 Beat AML trial (NCT03013998) showed revumenib in combination with venetoclax (Venclexta) and azacitidine (Vidaza) produced a composite complete remission rate of 96% in patients with newly diagnosed NPM1-mutant or KMT2A-rearranged AML, she states. Overall, these developments mark a significant advance in targeting acute leukemias and indicate that menin inhibitors are making promising strides in clinical research, Wang concludes.