Menin inhibitors are a new type of targeted therapy used to treat acute myeloid leukemia (AML). Recently, this class of medication has been approved by the U.S. Food and Drug Administration (FDA) for certain people with AML. Currently approved menin inhibitors include:
Revumenib (Revuforj, Syndax) is approved for relapsed and refractory AML with an NPM1 mutation or a KMT2A translocation.
Ziftomenib (Komzifti, Kura) for relapsed and refractory AML with an NPM1 mutation.
Two new menin inhibitors, bleximenib and enzomenib, are actively recruiting for clinical trials.
What is a menin inhibitor?
AML is a rare, aggressive form of blood cancer. In AML, immature cells called blasts multiply quickly and prevent healthy cells from functioning properly. Some acute leukemias are driven by certain cell (or protein) changes such as KMT2A rearrangement and NMP1 mutations.
Menin inhibitors are a type of targeted therapy. Menin refers to a type of protein. It is found in the nucleus of normal and cancerous cells. Menin interacts with the DNA in cells, which helps the cells develop normally. Menin inhibitors block this protein, which stops specific leukemia-causing genes from activating.
What is KMT2A rearrangement?
KMT2A is a gene that helps regulate gene expression. Research has shown that about 10% of acute leukemia cases have change to KMT2A called a KMT2A rearrangement or KMT2A translocation. It is associated with high rates of relapse in AML.
What is an NPM1 mutations?
NPM1 is a gene that supports the development of a protein responsible for DNA repair and regulating cell function. Changes in the NPM1 gene lead to an uncontrolled growth of white blood cells. NPM1 Mutations are present in about 30% to 40% of adult AML cases and 2% to -8% of childhood AML cases.
How do KMT2A and NPM1 changes affect menin?
Each of these proteins interacts with menin, a protein found in human cells that suppresses tumors. They can can cause menin not to function properly, leading to uncontrolled cell growth.
Menin inhibitors block the interaction between certain mutated proteins in AML. Blocking menin leads to a down regulation (a decrease in receptors) of cells associated with leukemia.
Revumenib (Revuforj): What it is and how it's used
Revumenib is a menin inhibitor. It was first approved by the U.S. FDA on November 15, 2024 for relapsed or refractory AML with a KMT2A translocation. On October 24, 2025, it was also approved for relapsed or refractory AML with an NPM1 mutation. It is approved to treat adults and children age one year and older who have no other treatment options. It is an oral therapy.
Revumenib is also used to treat acute lymphocytic leukemia (ALL).
Ziftomenib (Komzifti): What it is and how it's used
Ziftomenib is the second menin inhibitor approved by the FDA. It was approved on November 13, 2025 to treat relapsed and refractory AML with an NPM1 mutation.
What are common side effects of menin inhibitors?
As with many cancer treatments, revumenib and ziftomenib can cause side effects that range from mild to more serious and can vary from person to person. The most common serious side effect of menin inhibitors is differentiation syndrome, which is inflammation caused by an increased release of cytokines. It happens in 10% to 15% of patients.
Another serious side effect of menin inhibitors is QTc prolongation. This is a heart rhythm problem. Symptoms of QTc prolongation include dizziness, fainting, heart palpitations, and seizures. QTc prlongation happens more frequently with revumenib.
Other side effects of menin inhibitors are:
GI Symptoms (nausea, vomiting, diarrhea)
Blood count changes (cytopenia and neutropenia)
Muscle and bone pain
Infections
Always let your doctor know about any new or worsening side effects that you experience so that your care team can address them early.
Frequently asked questions about menin inhibitors
How does a menin inhibitor work?
Menin inhibitors block the protein menin. This protein is found in the nucleus of healthy and cancerous cells. When menin is blocked, it stops specific mutations from leading to leukemia cell development.
Are menin inhibitors FDA approved?
Yes, there are two FDA-approved menin inhibitors: revumenib (Revuforj) and zifotomenib (Komzifti).
What are the side effects of using menin inhibitors?
Side effects of menin inhibitors include: differentiation syndrome, QTc prolongation, nausea, vomiting, diarrhea, cytopenia, neutropenia, muscle and bone pain, and infections.
Watch a HealthTree webinar about menin inhibitors
In a recent HealthTree webinar, Dr. Eunice Wang, MD, an oncologist/hematologist at Roswell Park Comprehensive Cancer Center, presented on menin inhibitors. She shared that researchers are still investigating whether the drugs are effective for people without these specific mutations but that “current data suggests menin inhibitors are perhaps most effective in patients that have these biological identities.”
Menin inhibitors are a promising treatment for certain types of AML and ongoing research will help us better understand all of the potential benefits.
Watch Menin Inhibitors Explained
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