On October 24, 2025, the U.S. Food and Drug Administration (FDA) approved revumenib (Revuforj®) for patients 1-year-old and older who have leukemia that has come back after treatment and whose cancer carries a molecular change called an NPM1 mutation. In November 2024, the drug had been approved for treating the same class of patients whose cancer carries another molecular change, called a KMT2A translocation.
Revumenib, which was developed based on research conducted at Memorial Sloan Kettering Cancer Center (MSK), is the first drug in a new class of drugs called menin inhibitors to receive FDA approval. The trial that brought about the drug’s approval was led by Eytan Stein, MD, Chief of the Leukemia Service at MSK and an expert in early drug development.
“Revumenib is currently the only targeted treatment option for adult and pediatric patients who have relapsed or refractory acute leukemia caused by these rearrangements and mutations,” Dr. Stein says. “This subset of leukemia is seen in pediatric patients as well as in patients whose acute myeloid leukemia (AML) has arisen as a result of exposure to cytotoxic chemotherapy for another cancer.” These changes can also be found in children and adults with acute lymphoblastic leukemia (ALL).
Positive Leukemia Trial Results Using Menin Inhibitors
Among patients with a KMT2A rearrangement or an NPM1 mutation, 63% of patients respond to the drug, according to the study led by Dr. Stein and published in August 2024 in the Journal of Clinical Oncology. This trial was the first-ever clinical study of revumenib, and its phase 2 portion led to the drug’s FDA approvals.
“People with these types of alterations tend to have very aggressive disease,” says Dr. Stein, who directs MSK’s Program for Drug Development in Leukemia. “What we’ve seen with this drug is very promising, especially for this patient population.”
Menin Inhibitors Are a New Targeted Therapy for Leukemia in Children and Adults
The FDA evaluated data from 104 adult and pediatric patients in the trial, called AUGMENT-101, which was a multicenter, combined phase 1/2 trial. All of the enrolled patients had seen their leukemia come back after other treatments or had never responded well to traditional chemotherapy drugs in the first place.
KMT2A translocations and NPM1 mutations allow a protein called menin to drive cancer growth. By blocking the interaction between menin and other proteins, revumenib turns leukemia cells back into normal blood cells. “With revumenib, we will be able to get more patients with these genetic changes into remission so that they are then able to receive a stem cell or bone marrow transplant (BMT),” Dr. Stein says.
The early research on menin inhibitors was done by Scott Armstrong, MD, PhD, when he worked at MSK in the mid-2010s. Also participating in that research was leukemia specialist and physician-scientist Ross Levine, MD, MSK’s Chief Scientific Officer.
How One Patient Benefitted From Revumenib After His Cancer Came Back
When Michael Rosensweig learned in May 2021 that his AML had returned for a fourth time, it was difficult news to receive. He had been in remission for more than eight years.
This time, though, he had an option for a new and less grueling treatment. Rather than face another round of intensive chemotherapy requiring weeks of hospitalization, Michael found out that he qualified for the groundbreaking clinical trial of revumenib, which at the time was an experimental targeted therapy.
Revumenib Leads to a Better Quality of Life During Treatment for Leukemia
Revumenib is a pill that’s taken at home. “Being able to do treatment from home and just be normal for a while was nice, as opposed to being stuck in a hospital bed for months,” Michael says. “The drug did what it was supposed to do and was much easier on my body.”
Michael says he experienced no side effects, which was a relief compared with his earlier chemotherapy treatments. Overall, the side effects observed in the trial were not serious, and no patients had to drop out because of them.
“Menin inhibitors appear to be very well tolerated and are easy to take,” Dr. Stein says. “This is everything you want in a targeted therapy.”
Revumenib Offers More Options for Treating Aggressive Leukemias
After receiving revumenib, Michael went on to receive a BMT — his fourth — in October 2021. It was performed by hematologic oncologist Sergio Giralt, MD, who is the Deputy Division Head of MSK’s Division of Hematologic Malignancies. Michael received stem cells from an unrelated donor who was found in a public registry. A software engineer, he was first diagnosed with AML when he was a junior at the Massachusetts Institute of Technology. Four years after treatment, he continues to do well.
“The ultimate goal of these new treatments is to cure our patients,” Dr. Stein says. “For many, a transplant may be the best option. But for others, we hope to eventually develop combination therapies that will help to avoid, or get around, drug resistance.”
Understanding How Resistance to Revumenib Develops
An earlier paper, published in Nature in March 2023, described the genetic changes in leukemia that led to drug resistance. This research used patient samples as well as cells grown in the lab. The co-senior authors of that study were Dr. Armstrong, Dr. Levine, and MSK leukemia specialist and early drug development specialist Sheng Cai, MD, PhD.
“The level of response that we saw in patients enrolled in the trial was terrific, but not 100%. Whenever we test the efficacy of a novel cancer therapy by itself, we anticipate resistance mechanisms in this setting,” Dr. Cai says. “What these studies teach us — in particular, when these leukemias are forced to mutate to evade this drug — is that we are, in fact, getting to the Achilles’ heel of this aggressive disease.”
“That is a powerful lesson,” he adds, “and this research offers new opportunities to develop strategies to overcome this resistance, which is the next frontier in targeted therapies.”
Authors, Funding, Disclosures
The revumenib trial was funded by Syndax Pharmaceuticals.
Dr. Stein’s disclosures are as follows: Foghorn Therapeutics: Consultancy; Blueprint Medicines: Consultancy; Gilead Sciences, Inc.: Consultancy; Abbvie: Consultancy; Janssen Pharmaceuticals: Consultancy; Genentech: Consultancy; Jazz Pharmaceuticals: Consultancy; Bristol Myers Squibb: Consultancy; Celgene: Consultancy; PinotBio: Consultancy; Daiichi Sankyo: Consultancy; Astellas: Consultancy; Novartis: Consultancy; Agios Pharmaceuticals, Inc: Consultancy; Syros Pharmaceuticals, Inc.: Consultancy; Syndax Pharmaceuticals: Consultancy.
Dr. Cai discloses the following relationships and financial interests: Dava Oncology (Provision of Services); Imago Biosciences (Ownership/Equity Interests; Provision of Services [uncompensated]).
