Dr Erba on the FDA Approval of Ziftomenib in NMP1-Mutant Relapsed/Refractory AML

"In our study, we had patients achieving remission after single-agent ziftomenib who were able to then transition and proceed with allogeneic transplant, which would be the only potentially curative option for this group of patients."

Harry Erba, MD, PhD, professor of medicine in the Division of Hematologic Malignancies and Cellular Therapy, Department of Medicine; director of the Leukemia Program; and director of Phase I Development in Hematologic Malignancies at Duke Cancer Institute, discusses the significance of the November 2025 FDA approval of ziftomenib (Komzifti) for patients with relapsed/refractory acute myeloid leukemia (AML) who harbor a susceptible NPM1 mutation and have no satisfactory alternative treatment options.¹

This regulatory decision was supported by data from the phase 1/2 KOMET-001 trial (NCT04067336), which met its primary end point of complete remission (CR) plus CR with full or partial hematologic recovery (CRh) rate with single-agent ziftomenib. The agent produced a CR plus CRh rate of 21.4% (95% CI, 14.2%-30.2%) at a median follow-up of 4.2 months (range, 0.1-41.2). The median duration of CR plus CRh was 5 months (95% CI, 1.9-8.1), with individual CR and CRh rates reported as 17.0% (95% CI, 10.5%-25.2%) and 4.5% (95% CI, 1.5%-10.1%), respectively. Additionally, among patients who were transfusion-dependent at baseline (n = 66), 21.2% achieved red blood cell and platelet transfusion independence during any 56-day period after baseline. In evaluable patients who were transfusion-independent at baseline (n = 46), patients remained transfusion independent during any 56-day period after baseline.

Although intensive chemotherapy regimens are highly effective in fit, younger patients with this favorable subset of AML, relapses still occur, Erba noted. Similarly, relapse is common in older patients with NPM1 mutations who do not display FLT3 ITD or RAS mutations often due to unfavorable karyotypes or mutations suggestive of prior myelodysplastic syndrome, he added.

For these patients who relapse, having a drug such as ziftomenib available is crucial, especially because prior exposure to venetoclax (Venclexta) did not appear to impact outcomes with single-agent ziftomenib, Erba noted. Achieving remission with this drug provides patients a chance to transition to allogeneic transplant, which is the only potentially curative option, Erba concluded.