Ziftomenib Plus 7+3 Yields Strong Responses in NPM1-Mutated, KMT2A-Rearranged AML: Eunice S. Wang, MD

Earlier this month, a study published in Blood reported updated results from the relapsed/refractory (R/R) NPM1-mutated acute myeloid leukemia (NPM1-m AML) cohort of KOMET-007 (NCT05735184), a Phase 1A/B trial evaluating ziftomenib 600 mg in combination with venetoclax and azacitidine. It demonstrated that nearly two-thirds of adults with R/R NPM1-m AML experienced clinically meaningful, deep, and durable responses with a well-tolerated safety profile.

Building on these findings, long-term results from the frontline arm of KOMET-007 evaluating ziftomenib in combination with intensive chemotherapy, particularly cytarabine plus daunorubicin (7+3), in patients with newly diagnosed NPM1-m or KMT2A-rearranged (KMT2A-r) AML will be presented at the European Hematology Association 2026 Congress in Stockholm, Sweden. The American Journal of Managed Care^® spoke with Eunice S. Wang, MD, one of the trial’s investigators and chief of leukemia at Roswell Park Comprehensive Cancer Center, about the importance of these findings ahead of the meeting .

The frontline cohort enrolled 99 patients, including 49 with NPM1 mutations and 50 with KMT2A rearrangements, representing the largest clinical dataset of these molecular subsets treated with a menin inhibitor plus intensive chemotherapy to date. Against an expected response rate of approximately 67% to 70% with 7+3 alone, Wang noted that the combination produced an overall response rate of approximately 93%.

NPM1-m patients achieved a complete remission/complete remission with a partial hematologic recovery rate of approximately 98%, whereas KMT2A-r patients exceeded 90%. At more than 1 year of follow-up, median overall survival was approximately 12 months in the KMT2A-r group, but it was not reached in the NPM1-m cohort.

Wang added that measurable residual disease (MRD) negativity rates of 70% to 80% were achieved by both central and local assays, reflecting meaningful depth of remission. Because roughly half of patients in morphologic remission after intensive chemotherapy ultimately relapse, MRD negativity serves as a key early indicator of durability, particularly in NPM1-m disease; consequently, it is planned as a primary end point in future phase 3 trials.

Wang concluded by highlighting that the safety profile was consistent with intensive chemotherapy alone. Myelosuppression was the dominant toxicity, with most patients recovering neutrophil and platelet counts within 30 days, and no excess cytopenias were observed. Menin inhibitor-specific toxicities were rare, as differentiation syndrome occurred in 2 to 3 patients, all managed with early steroids, and only one case of QTc prolongation was considered potentially ziftomenib-related.

“Those don't appear to be major side effects that would be unreasonable to be able to be managed in a common practice setting,” Wang said.