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The FDA granted to the menin inhibitor revumenib (Revuforj) for adults and children 1 year and older with relapsed/refractory acute leukemia and a lysine methyltransferase 2A gene (KMT2A) translocation.

Support for the approval came from the phase I/II AUGMENT-101 trial, which evaluated single-agent revumenib in 104 children and adults with previously treated acute leukemia associated with KTM2A rearrangements.

The primary endpoint was complete response with or without hematologic recovery. The data showed a complete response rate of 21.2%, which was associated with a median response duration of 6.4 months. Additionally, 12 of 83 transfusion-dependent patients achieved freedom from red blood cell or platelet transfusions. Among 21 patients who were transfusion independent at baseline, 10 (48%) maintained that status during any 56-day period.

"After achieving response, 40% of responders were able to go to allogeneic stem cell transplant, which is really our ultimate goal for someone with relapsed/refractory leukemia," said Ibrahim Aldoss, MD, of City of Hope in Duarte, California, during a presentation at the 2023 American Society of Hematology meeting. "It's a disease with unmet therapeutic needs. These patients have high risk of relapse after transplant and after chemotherapy."

At the time, no KMT2A-targeted therapies had FDA approval.

Adverse reactions occurring in ≥20% of patients consisted of hemorrhage, nausea, increased phosphate, musculoskeletal pain, infection, increased aspartate aminotransferase, febrile neutropenia, increased alanine aminotransferase, increased intact parathyroid hormone, bacterial infection, diarrhea, differentiation syndrome, electrocardiogram QT prolonged, decreased phosphate, increased triglycerides, decreased potassium, decreased appetite, constipation, edema, viral infection, fatigue, and increased alkaline phosphatase.

"The FDA approval of the first menin inhibitor is a major breakthrough for patients with [relapsed/refractory] acute leukemia with a KMT2A translocation, a genetic alteration associated with a very poor prognosis," said Ghayas C. Issa, MD, of the University of Texas MD Anderson Cancer Center in Houston, in a from Syndax Pharmaceuticals. "The significant clinical benefit and robust efficacy seen with Revuforj represents a substantial improvement over what has been historically observed in these patients with previously available therapies and has the potential to be an important new treatment option for patients."

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