The U.S. Food and Drug Administration (FDA) has granted accelerated approval to revumenib (Revuforj) for the treatment of adult and pediatric patients aged 1 year and older with relapsed or refractory acute leukemia harboring a KMT2A translocation. This approval marks a significant advancement in the treatment of this aggressive form of leukemia, offering a new therapeutic option for patients with limited alternatives. The decision was based on data from the AUGMENT-101 trial (SNDX-5613-0700; NCT04065399), a single-arm, open-label, multicenter study.
The AUGMENT-101 trial enrolled 104 adult and pediatric patients (at least 30 days old) with relapsed or refractory KMT2A-translocated acute leukemia. Patients with an 11q23 partial tandem duplication were excluded from the trial. Revumenib was administered until disease progression, unacceptable toxicity, failure to achieve morphological leukemia-free state by 4 cycles of treatment, or hematopoietic stem cell transplantation.
The primary endpoint was the rate of complete remission (CR) plus complete remission with partial hematologic recovery (CRh). Results showed a CR+CRh rate of 21.2% (95% CI, 13.8-30.3). The median duration of CR+CRh was 6.4 months (95% CI, 2.7–not estimable). The median time to CR or CRh was 1.9 months (range, 0.9-5.6) in the 22 patients who achieved a CR or CRh.
Impact on Transfusion Independence
An important secondary endpoint was the conversion from transfusion dependence to independence. Among 83 patients who were dependent on red blood cell (RBC) and/or platelet transfusions at baseline, 14% became RBC-independent and platelet transfusion–independent during a 56-day post-baseline period. Of the 21 patients who were independent of both RBC and platelet transfusions at baseline, 48% of them remained transfusion independent during any 56-day post-baseline period.
Safety Profile
The most common adverse effects, occurring in at least 20% of patients, included 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. These adverse events highlight the importance of careful monitoring and management during revumenib treatment.
This approval represents a significant step forward in the treatment of relapsed/refractory KMT2A-translocated acute leukemia, offering a potentially life-extending option for patients with this challenging disease.
