Revumenib Approved for KMT2A Translocation Leukemia

The US Food and Drug Administration has approved revumenib (Revuforj — Syndax Pharmaceuticals) for relapsed or refractory acute leukemia with a KMT2A gene translocation in adult and pediatric patients 1 year or older.

The approval makes the oral small-molecule menin inhibitor the first pharmaceutical to carry the indication. It blocks the binding of menin to mutated KMT2A fusion proteins, tamping down the process that leads to the disease.

Although a relatively uncommon form of leukemia, KMT2A rearrangements are a major driver of acute leukemia in infants.

Approval was based on a single-arm of the open-label AUGMENT-101 trial with 104 adult and pediatric patients with the mutation. Pediatric patients were at least 30 days old.

The rate of complete remission (CR) plus CR with partial hematologic recovery was 21.2% (22 patients) with a median duration of 6.4 months. The median time to remission was 1.9 months.

Eighty-three patients required blood cell and/or platelet transfusions at baseline; 12 (14%) did not need transfusions for 56 days afterward. Of the 21 who were transfusion-free at baseline, 10 (48%) remained so over the same period.

The most common adverse reactions in 20% or more of patients were 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 recommended dose varies by weight and concomitant use of strong CYP3A4 inhibitors. Due to an anticipated delay in commercial availability, the lowest strength dose of revumenib will be available through an expanded access program for patients who weigh

M. Alexander Otto is a physician assistant with a master’s degree in medical science and a journalism degree from Newhouse. He is an award-winning medical journalist who worked for several major news outlets before joining Medscape Medical News. Alex is also an MIT Knight Science Journalism fellow. Email: aotto@mdedge.com