The Food and Drug Administration (FDA) has granted approval to Revuforj (revumenib) for the treatment of adult and pediatric patients aged 1 year and older with relapsed or refractory acute leukemia, specifically those harboring a KMT2A translocation. This approval addresses a critical unmet need in patients with this aggressive form of leukemia who have limited treatment options.
The approval is based on data from the AUGMENT-101 trial, a study that enrolled 104 adult and pediatric patients with relapsed or refractory acute leukemia and a KMT2A translocation. Patients with an 11q23 partial tandem duplication were excluded from the trial. Revumenib was administered until unacceptable toxicity, disease progression, hematopoietic stem cell transplantation, or failure to achieve morphological leukemia-free state after four cycles.
The primary efficacy endpoint was the rate of complete remission (CR) plus complete remission with partial hematological recovery (CRh). Results from the AUGMENT-101 trial showed that 21.2% of patients achieved CR+CRh, with a median duration of 6.4 months. The median time to CR or CRh was 1.9 months.
Furthermore, the trial assessed transfusion independence. Of the 83 patients who were dependent on red blood cell and/or platelet transfusions at baseline, 14% achieved independence from both red blood cell and platelet transfusions during the 56-day period following the start of treatment. Among the 21 patients who were independent of transfusions at baseline, 48% remained transfusion-independent during the same period.
The most common adverse reactions, occurring in at least 20% of patients, included nausea, bleeding, musculoskeletal pain, hyperphosphatemia, increased aspartate aminotransferase, infection, febrile neutropenia, increased intact parathyroid hormone, increased alanine aminotransferase, diarrhea, bacterial infection, QT prolongation, differentiation syndrome, hypertriglyceridemia, hypophosphatemia, hypokalemia, constipation, decreased appetite, fatigue, viral infection, and increased alkaline phosphatase.
The FDA has specified that the recommended dose of Revuforj varies based on patient weight and concomitant use of strong CYP3A4 inhibitors. Due to an anticipated delay in the commercial availability of the lowest-dose strength of Revuforj, an expanded access program will be implemented to ensure access for patients weighing less than 40 kg.
