Revumenib is approved by the USFDA for relapsed or refractory acute leukemia with a KMT2A translocation

On November 15, 2024, the Food and Drug Administration sanctioned revumenib (Revuforj, Syndax Pharmaceuticals, Inc.), a menin inhibitor, for relapsed or refractory acute leukemia characterized by a lysine methyltransferase 2A gene (KMT2A) translocation in adult and pediatric patients aged 1 year and older.

Efficacy and Safety

The efficacy was assessed in a single-arm cohort of an open-label, multicenter trial (SNDX-5613-0700, NCT04065399; AUGMENT-101) involving 104 adult and pediatric patients (minimum age of 30 days) diagnosed with relapsed or refractory acute leukemia featuring a KMT2A translocation. Patients exhibiting an 11q23 partial tandem duplication were eliminated. Revumenib was supplied until disease progression, intolerable toxicity, failure to attain a morphological leukemia-free state after four therapy cycles, or hematopoietic stem cell transplantation (HSCT).

The primary effectiveness outcome indicators included complete remission (CR) and complete remission with partial hematologic recovery (CRh), the duration of CR and CRh, and the transition from transfusion dependency to independence. The CR+CRh rate was 21.2% (95% CI: 13.8, 30.3), and the median duration of CR+CRh was 6.4 months (95% CI: 2.7, not estimable). Among the 22 patients who attained complete remission (CR) or complete remission with partial hematologic recovery (CRh), the median duration to achieve CR or CRh was 1.9 months (range: 0.9 to 5.6 months).

Of the 83 patients reliant on red blood cell (RBC) and platelet transfusions at baseline, 12 (14%) achieved independence from these transfusions over any 56-day period following the baseline. Among the 21 patients who were independent of both RBC and platelet transfusions at baseline, 10 (48%) maintained transfusion independence over the 56-day period following the baseline.

The most prevalent adverse reactions (≥20%) included hemorrhage, nausea, elevated phosphate levels, musculoskeletal pain, infection, increased aspartate aminotransferase, febrile neutropenia, elevated alanine aminotransferase, heightened intact parathyroid hormone, bacterial infection, diarrhea, differentiation syndrome, prolonged electrocardiogram QT interval, decreased phosphate levels, increased triglycerides, reduced potassium levels, diminished appetite, constipation, edema, viral infection, fatigue, and elevated alkaline phosphatase.

The advised dosage of revumenib is contingent upon patient weight and the concurrent administration of potent CYP3A4 inhibitors. Refer to the prescription instructions for detailed dose guidelines. Owing to a projected delay in the commercial release of the lowest dosage of revumenib, intended for patients weighing less than 40 kg, revumenib will be accessible via an expanded access program to facilitate dosing for this patient population (details available here: NCT05918913).