How Do Menin Inhibitors Work?

Menin inhibitors are medications used to treat patients one year and older, with relapsed or refractory acute leukemia, a type of blood cancer. Menin inhibitors are used to treat leukemia that has translocation of a gene known as lysine methyltransferase 2A (KMT2A). Menin inhibitors work by preventing interaction between menin and KMT2A proteins, which drives cancer cell growth in leukemia.

Menin is a nuclear scaffold protein, which has many functions, including the regulation of bone marrow (myeloid) and blood cell growth (hematopoiesis). Nuclear scaffold proteins are a network of protein fibers around the cell nucleus that provide structural support, and regulate many signaling pathways and gene expression.

The KMT2A protein encoded by KMT2A gene plays an important role in hematopoiesis. Translocation or rearrangement of this gene (KMT2Ar) causes production of fusion proteins that cause uncontrolled growth and proliferation of myeloid and blood cells. KMT2Ar is found in approximately 10% of acute myeloid leukemia (AML), 70% to 80% of infant leukemias, and 70% of therapy-related leukemias.

The KMT2Ar fusion proteins need to bind to the nuclear scaffold protein menin, to upregulate the signals for the proliferation of the cancer cells. Menin inhibitors block the expression of the abnormal KMT2Ar gene, which prevents the formation of fusion proteins and the growth and proliferation of the leukemia cells, and instead allows the production of normal blood cells.

Currently, the first and only drug that has been approved by the FDA in the menin inhibitors class of drugs is revumenib (Revuforj).

Menin inhibitors are oral tablets approved by the FDA to treat adults and children one year and older who have relapsed or refractory acute leukemia with a lysine methyltransferase 2A (KMT2A) gene translocation.

Common side effects of menin inhibitors include the following:

• Bleeding (hemorrhage)
• Blood clot formation in blood vessels (thrombosis)
• Nausea
• Vomiting
• Diarrhea
• Constipation
• Musculoskeletal pain
• Infections
• Bacterial infections
• Viral infections
• Low count of neutrophil immune cells (neutropenia)
• Neutropenia-induced fever (febrile neutropenia)
• Abnormally high white blood cell count (leukocytosis)
• Increase in phosphate
• Decrease in phosphate
• Decrease in potassium
• Increase in calcium
• Increase in liver enzymes:
• Aspartate aminotransferase
• Alanine aminotransferase
• Alkaline phosphatase
• Increase in parathyroid hormone, intact
• Increase in triglycerides
• Increase in cholesterol
• Increase in creatinine
• Differentiation syndrome, a complication that leads to severe, sometimes life-threatening reaction to anticancer treatment
• Heart rhythm disturbance (QT prolongation)
• Reduced appetite
• Swelling from fluid retention (edema)
• Fatigue
• Fluid around the heart (pericardial effusion)
• Heart failure
• Rapid contractions of the ventricles (ventricular tachycardia)
• Cardiac arrest
• Overactive parathyroid (hyperparathyroidism)
• Abdominal pain
• Kidney impairment
• Low blood sodium level (hyponatremia)
• High blood potassium (hyperkalemia)
• Cataract
• Taste disorder
• Headache
• Fainting (syncope)
• Abnormal skin sensations (paresthesia)
• Rash
• Drug hypersensitivity
• Sudden death

Information contained herein is not intended to cover all possible side effects, precautions, warnings, drug interactions, allergic reactions, or adverse effects. Check with your doctor or pharmacist to make sure these drugs do not cause any harm when you take them along with other medicines. Never stop taking your medication and never change your dose or frequency without consulting your doctor.

Generic and brand names of menin inhibitors include:

• Revuforj
• revumenib