FDA Grants Approval to Revumenib for Patients With R/R Acute Leukemia With KMT2A Translocation

On November 15, 2024, the US Food and Drug Administration (FDA) approved menin inhibitor revumenib for adult and pediatric patients 1 year and older with relapsed/refractory acute leukemia with a lysine methyltransferase 2A gene (KMT2A) translocation.

For this approval, revumenib’s efficacy was evaluated in a single-arm cohort of an open-label, multicenter trial (SNDX-5613-0700, NCT04065399; AUGMENT-101) in 104 adult and pediatric patients at least 30 days old with R/R acute leukemia with a KMT2A translocation. Patients with an 11q23 partial tandem duplication were excluded. 

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 (HSCT).

The main efficacy outcome measures were complete remission (CR) plus CR with partial hematologic recovery (CRh), the duration of CR+CRh, and conversion from transfusion dependence to independence. The CR+CRh rate was 21.2% (95% CI; 13.8 to 30.3), and the median CR+CRh duration was 6.4 months (95% CI; 2.7 to not estimable). Of the 22 patients achieving CR or CRh, the median time to CR or CRh was 1.9 months (range: 0.9, 5.6 months). Among the 83 patients dependent on red blood cell (RBC) and/or platelet transfusions at baseline, 12 (14%) became independent of RBC and platelet transfusions during any 56-day post-baseline period. Of the 21 patients independent of both RBC and platelet transfusions at baseline, 10 (48%) remained transfusion independent during any 56-day post-baseline period.

Investigators found the most frequent adverse events (≥20%) to be 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.

Source:

US Food and Drug Administration. FDA approves revumenib for relapsed or refractory acute leukemia with a KMT2A translocation. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-revumenib-relapsed-or-refractory-acute-leukemia-kmt2a-translocation. Accessed November 17, 2024.