The FDA has granted approval to revumenib (Revuforj) for the treatment of adult and pediatric patients aged 1 year and older with relapsed or refractory acute leukemia that harbors a KMT2A translocation. This approval marks a significant advancement in the treatment of this aggressive form of leukemia, which is associated with a poor prognosis.
The approval was based on data from the phase 1/2 AUGMENT-101 study (NCT04065399), a multicenter, open-label trial evaluating the efficacy and safety of revumenib in patients with relapsed or refractory acute leukemia with a KMT2A translocation. The study enrolled both adult and pediatric patients.
Efficacy of Revumenib
The AUGMENT-101 study demonstrated a complete remission (CR) plus CR with partial hematologic recovery (CRh) rate of 21.2% (95% CI, 13.8%-30.3%) in patients treated with revumenib (n = 104). The median duration of CR+CRh was 6.4 months (95% CI, 2.7-not estimable). In the subset of patients who achieved a CR or CRh (n = 22), the median time to response was 1.9 months (range, 0.9-5.6).
Additional findings from the study indicated that 14% of patients who were dependent on red blood cell (RBC) and platelet transfusions at baseline achieved independence during any 56-day post-baseline period. Furthermore, 48% of patients who were independent of transfusions at baseline remained independent during the study period.
Safety Profile
The safety of revumenib was evaluated in 104 adult patients and 31 pediatric patients. The median duration of exposure to revumenib was 2.3 months (range, <1-23). Common adverse events (≥20%) included hemorrhage (53%), nausea (51%), musculoskeletal pain (42%), infection (41%), febrile neutropenia (35%), bacterial infection (31%), diarrhea (30%), differentiation syndrome (29%), and prolonged electrocardiogram QT (29%).
Serious adverse events were reported in 73% of patients, and 3% experienced fatal adverse events, including differentiation syndrome (n = 2), hemorrhage (n = 1), and sudden death (n = 1).
Expert Commentary
"The FDA approval of the first menin inhibitor is a major breakthrough for patients with R/R acute leukemia with a KMT2A translocation, a genetic alteration associated with a very poor prognosis," said Ghayas C. Issa, MD, associate professor of leukemia at The University of Texas MD Anderson Cancer Center. "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."
Study Design
The AUGMENT-101 trial enrolled patients aged 30 days and older with relapsed or refractory acute leukemia harboring a KMT2A translocation. Patients were administered revumenib orally twice daily at a dose approximately equivalent to 160 mg in adults, along with a strong CYP3A4 inhibitor. Treatment continued until disease progression, unacceptable toxicity, failure to achieve a morphological leukemia-free state by 4 cycles, or hematopoietic stem cell transplantation. The primary endpoint was the CR+CRh rate.
