The U.S. Food and Drug Administration (FDA) approved revumenib, a first-in-class oral menin inhibitor, for the treatment of adults and children one year and older with relapsed or refractory acute myeloid leukemia (AML) with NPM1 gene mutations. Revumenib was first approved in November 2024 for patients with AML harboring a KMT2A translocation.
While KMT2A mutations are somewhat rare in AML, NPM1 mutations are much more common. With this most recent approval, up to 40% of patients with AML will have access to this novel medicine as an option for treatment.
"It is personally satisfying to see that the hard work of our scientists has led not only to a novel approach to AML therapy but also to its availability to many more patients," says Dr. Scott Armstrong, senior vice president for Drug Discovery and Chief Research Strategy Officer at Dana-Farber Cancer Institute.
AML is diagnosed in more than 20,000 people in the US each year and has a 5-year survival rate of approximately 30%. NPM1 mutations are the most common gene mutations in adults with AML, occurring in up to 30% of patients, and can be associated with a poor prognosis. Prior to this approval, there were few effective treatment options for this patient group after initial relapse.
More than twenty years of Dana-Farber/Boston Children's Hospital research contributed directly to the initial discovery, development, and approval of revumenib. Research leading to the expansion of its reach began in 2016, when Armstrong and his team hypothesized that AML with NPM1 mutations might also depend on menin for survival. If true, this form of cancer would also be vulnerable to treatment with revumenib. His lab later confirmed the idea, and additional research led to the initiation of clinical testing.
The approval for patients with NPM1 mutations is based on results from the phase II AUGMENT-101 clinical trial, which was led at Dana-Farber by Dr. Richard Stone, director of Translational Research, Leukemia Division, Medical Oncology and Dana-Farber Chief of Staff, and Dr. Jessica Pollard, a pediatric oncologist in the Dana-Farber/Boston Children's Cancer and Blood Disorders Center, and Clinical Director of the pediatric Hematologic Malignancies Program.
The trial included children and adults with relapsed or refractory AML, many of whom had received several lines of treatment. A single-arm cohort of patients with NPM1 mutations were treated with revumenib. Among them, 23.1% experienced a complete remission with partial recovery of blood counts, called partial hematologic recovery. Mean duration of the complete response and partial hematologic recovery was 4.5 months.
"This approval is exciting and validates this approach as a new therapy," says Armstrong. "We know, however, that combinations are likely to be more effective, and trials of multiple combinations with revumenib are underway."
"This is a monumental step forward as NPM1 mutations represent about one-third of patients," adds Dr. Jacqueline Garcia, a medical oncologist in the Division of Leukemia. "We have exciting combination clinical trials for patients with newly diagnosed and with persistent disease-called measurable residual disease or leftover microscopic disease-as the next step to build on these compelling single agent data."
The AUGMENT-101 study was funded by Syndax Pharmaceutical, Inc.
