The U.S. Food and Drug Administration (FDA) has granted approval to revumenib (Revuforj, Syndax Pharmaceuticals) for the treatment of adult and pediatric patients aged one year and older with relapsed or refractory acute leukemia who harbor a lysine methyltransferase 2A (KMT2A) translocation. This approval marks a significant advancement for patients with this aggressive form of leukemia, characterized by poor prognosis and limited treatment options.
The approval was based on data from the Phase 1/Phase 2 AUGMENT-101 trial, which 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 study. Revumenib was administered until disease progression, unacceptable toxicity, failure to achieve morphological leukemia-free state after four cycles, or receipt of hematopoietic stem cell transplantation.
The primary efficacy outcomes were complete remission (CR), complete remission with partial hematologic recovery (CRh), duration of CR and CRh, and conversion from transfusion dependence to independence. The study demonstrated a CR+CRh rate of 21.2% (95% CI, 13.8-30.3), with a median CR+CRh duration of 6.4 months (95% CI, 2.7 to not estimable). Among the 22 patients who achieved CR or CRh, the median time to response was 1.9 months (range, 0.9-5.6 months).
Transfusion Independence
Of the 83 patients who were dependent on transfusions at baseline, 12 (14%) achieved transfusion independence during any 56-day post-baseline period. Among the 21 patients who were independent of transfusions at baseline, 10 (48%) remained transfusion independent during any 56-day post-baseline period.
Expert Commentary
"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," said Ghayas C. Issa, MD, associate professor of leukemia at The University of Texas MD Anderson Cancer Center.
Safety Profile
Adverse reactions occurring in at least 20% of study participants 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, QT prolongation, decreased phosphate, increased triglycerides, decreased potassium, decreased appetite, constipation, edema, viral infection, fatigue, and increased alkaline phosphatase.
Regulatory Context
The FDA had previously granted priority review, breakthrough therapy designation, and orphan drug designation to revumenib for this indication.
