Revumenib Approved for Relapsed or Refractory Acute Leukemia With a KMT2A Translocation
Expert Perspectives · Lyn Brook · 2024-11-18
The FDA has granted approval to revumenib (Revuforj®, Syndax Pharmaceuticals, Inc.), a menin inhibitor, for relapsed or refractory acute leukemia with a lysine methyltransferase 2A gene (KMT2A) translocation in adult and pediatric patients one year and older. This is the first approval of a menin inhibitor.
Why is the Approval of Revumenib Important?
“Revumenib, an oral, small molecule inhibitor of the menin-lysine methyltransferase 2A (KMT2A) interaction, showed promising efficacy and safety in a phase 1 study of heavily pretreated patients with KMT2A-rearranged (KMT2Ar) acute leukemia,” wrote Ghayas C. Issa, MD, a Medical Oncologist specializing in leukemia at The University of Texas, MD Anderson Cancer Center, and colleagues, in their published results of the AUGMENT-101 trial (NCT04065399), on which approval was based.
Evaluating Revumenib in the AUGMENT-101 Trial
Efficacy was measured in the phase 1/2, open-label trial which enrolled 104 adult and pediatric patients with relapsed or refractory acute leukemia with a KMT2A translocation. Patients were excluded from this study if they possessed an11q23 partial tandem duplication. Enrolled patients received revumenib until disease progression, unacceptable toxicity, failure to achieve morphological leukemia-free state by four cycles of treatment, or hematopoietic stem cell transplantation (HSCT).
The primary end points measured were complete response (CR) plus CR with partial hematologic recovery (CRh), the duration of CR plus CRh, and conversion from transfusion dependence to independence.
The rate of CR plus CRh was 21.2% in those receiving revumenib, and the median CR plus CRh duration was 6.4 months. Among the 22 patients who achieved CR or CRh, the median time to achievement was 1.9 months. Of the 83 patients who were dependent on red blood cell and/or platelet transfusions at baseline, 12 (14%) became independent of red blood cell and platelet transfusions during any 56-day post-baseline period. Of the 21 patients who were independent of red blood cell and platelet transfusions at baseline, 10 (48%) remained transfusion-independent during any 56-day post-baseline period.
Adverse Events
The most common adverse events experienced in ≥20% of those receiving revumenib 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.
Putting It Into Context
“Revumenib led to high remission rates with a predictable safety profile in relapsed/refractory KMT2Ar acute leukemia,” concluded Dr. Issa and colleagues. “To our knowledge, this trial represents the largest evaluation of a targeted therapy for these patients.”
Dosing Instructions
The recommended dosage of revumenib depends on the patient’s weight and concurrent use of strong CYP3A4 inhibitors; refer to the prescribing information for detailed dosage guidance. Since there may be a delay in the commercial availability of the lowest dose strength required for patients weighing less than 40 kg, revumenib will be accessible through an expanded access program to accommodate these patients.