Michael Rosensweig with Snow, photographed in the summer of 2020, before his latest disease recurrence
On November 15, 2024, 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 a KMT2A translocation.
Revumenib is the first drug in a new class 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 the first targeted treatment option for adult and pediatric patients with KMT2A-rearranged acute leukemia,” 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.”
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 a groundbreaking clinical trial (research study) of revumenib, an experimental targeted therapy. The drug, which is in a new class called menin inhibitors, was developed based on research conducted at Memorial Sloan Kettering Cancer Center (MSK). Revumenib is the first menin inhibitor to receive FDA approval.
Positive Leukemia Trial Results Using Menin Inhibitors
In August 2024, Dr. Stein published the pivotal results from the Phase 2 portion of the first-ever clinical trial of revumenib. This is the trial that led to the drug’s FDA approval. According to the findings, published in the Journal of Clinical Oncology, 63% of patients in the trial responded to the drug.
All patients in the study had a KMT2A rearrangement. These changes can be found in both children and adults with AML and acute lymphoblastic leukemia (ALL).
“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, as with Michael, or had never responded well to traditional chemotherapy drugs in the first place.
Dr. Eytan Stein led the clinical trial that resulted in revumenib’s FDA approval.
KMT2A translocations 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 the KMT2A rearrangement 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 Senior Vice President for Translational Research.
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. He is now doing 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
Another paper, published in Nature in March 2023, described the genetic changes in the 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 on 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.”
He adds: “That is a powerful lesson, and this research offers new opportunities to develop strategies to overcome this resistance, which is the next frontier in targeted therapies.”
