On November 15, 2024, the Food and Drug Administration sanctioned revumenib (Revuforj, Syndax Pharmaceuticals, Inc.), a menin inhibitor, for relapsed or refractory acute leukemia characterized by a lysine methyltransferase 2A gene (KMT2A) translocation in adult and pediatric patients aged 1 year and older.
Efficacy and Safety
The efficacy was assessed in a single-arm cohort of an open-label, multicenter trial (SNDX-5613-0700, NCT04065399; AUGMENT-101) involving 104 adult and pediatric patients (minimum age of 30 days) diagnosed with relapsed or refractory acute leukemia featuring a KMT2A translocation. Patients exhibiting an 11q23 partial tandem duplication were eliminated. Revumenib was supplied until disease progression, intolerable toxicity, failure to attain a morphological leukemia-free state after four therapy cycles, or hematopoietic stem cell transplantation (HSCT).
The primary effectiveness outcome indicators included complete remission (CR) and complete remission with partial hematologic recovery (CRh), the duration of CR and CRh, and the transition from transfusion dependency to independence. The CR+CRh rate was 21.2% (95% CI: 13.8, 30.3), and the median duration of CR+CRh was 6.4 months (95% CI: 2.7, not estimable). Among the 22 patients who attained complete remission (CR) or complete remission with partial hematologic recovery (CRh), the median duration to achieve CR or CRh was 1.9 months (range: 0.9 to 5.6 months).
Of the 83 patients reliant on red blood cell (RBC) and platelet transfusions at baseline, 12 (14%) achieved independence from these transfusions over any 56-day period following the baseline. Among the 21 patients who were independent of both RBC and platelet transfusions at baseline, 10 (48%) maintained transfusion independence over the 56-day period following the baseline.
The most prevalent adverse reactions (≥20%) included hemorrhage, nausea, elevated phosphate levels, musculoskeletal pain, infection, increased aspartate aminotransferase, febrile neutropenia, elevated alanine aminotransferase, heightened intact parathyroid hormone, bacterial infection, diarrhea, differentiation syndrome, prolonged electrocardiogram QT interval, decreased phosphate levels, increased triglycerides, reduced potassium levels, diminished appetite, constipation, edema, viral infection, fatigue, and elevated alkaline phosphatase.
The advised dosage of revumenib is contingent upon patient weight and the concurrent administration of potent CYP3A4 inhibitors. Refer to the prescription instructions for detailed dose guidelines. Owing to a projected delay in the commercial release of the lowest dosage of revumenib, intended for patients weighing less than 40 kg, revumenib will be accessible via an expanded access program to facilitate dosing for this patient population (details available here: NCT05918913).
Susan Hau is a distinguished researcher in the field of cancer cell therapy, with a particular focus on T cell-based approaches and cancer vaccines. Her work spans several innovative treatment modalities, including CAR T-cell therapy, TIL (Tumor-Infiltrating Lymphocyte) therapy, and NK (Natural Killer) cell therapy.
Hau's expertise lies in cancer cell biology, where she has made significant contributions to understanding the complex interactions between immune cells and tumors.
Her research aims to enhance the efficacy of immunotherapies by manipulating the tumor microenvironment and exploring novel ways to activate and direct immune responses against cancer cells.
Throughout her career, Hau has collaborated with leading professors and researchers in the field of cancer treatment, both in the United States and China.
These international experiences have broadened her perspective and contributed to her innovative approach to cancer therapy development.
Hau's work is particularly focused on addressing the challenges of treating advanced and metastatic cancers. She has been involved in clinical trials evaluating the safety and efficacy of various immunotherapy approaches, including the promising Gamma Delta T cell therapy.
