How does Gleevec (imatinib) work?

Gleevec, known generically as imatinib, works by slowing or stopping the growth of certain cancer cells. Gleevec inhibits (or blocks) specific enzymes in the body called tyrosine kinases. Tyrosine kinase enzymes are involved in many cell functions, including cell signaling (communication), growth, and division. Blocking these enzymes may help to slow cancer growth.

Gleevec (imatinib) inhibits tyrosine kinases associated with the BCR-ABL, PDGF (platelet-derived growth factor), SCF (stem cell factor) and the KIT protein. These enzymes are proteins that are involved in the development of blood cancers like chronic myelogenous leukemia (CML), acute lymphoblastic leukemia (ALL), certain skin cancers and some types of tumors of the stomach or intestine.

Related: Gleevec drug overview (side effects, warnings and dosage in detail)

Gleevec is classified as a tyrosine kinase inhibitor and is known as a targeted therapy. Targeted drugs are designed to work by focusing on a specific feature or mutation of the cancer cells that allows them to grow and multiply.

Gleevec, from Novartis Pharmaceuticals, was the first medicine approved by the FDA in 2001 to specifically block the BCR-ABL tyrosine kinase protein, a target for certain forms of leukemia. It is given as an oral tablet and is now available as a generic option.

In November 2024, Shorla Oncology announced the approval of Imkeldi (imatinib mesylate), an 80 mg/mL oral solution formulation of the approved kinase inhibitor imatinib (Gleevec). Imekeldi is a strawberry flavored oral solution that may be more convenient for patients who have difficulty swallowing tablets or who require specific dosing tailored to body surface area.

Which drugs are BCR-ABL tyrosine kinase inhibitors?

Drugs that target BCR-ABL and are known as tyrosine kinase inhibitors (TKIs) include:

• Imkeldi (imatinib)
• Gleevec (imatinib)
• Bosulif (bosutinib)
• Sprycel (dasatinib)
• Phyrago (dasatinib)
• Tasigna (nilotinib)
• Danziten (nilotinib)
• Iclusig (ponatinib)
• Scemblix (asciminib)

Your doctor can have a blood or bone marrow test performed to detect the presence of the BCR-ABL gene, or other genes or mutations that may be fueling the cancer growth.

What does imatinib (Gleevec) treat?

Imatinib (Gleevec) is approved by the FDA to treat:

• Certain phases of Philadelphia chromosome positive chronic myeloid leukemia (Ph+ CML)
• Certain phases of Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL)
• Myelodysplastic / myeloproliferative diseases
• Agressive systemic mastocytosis
• Dermatofibrosarcoma protuberans
• Hypereosinophilic syndrome (HES) and / or chronic eosinophilic leukemia (CEL)
• KIT+ gastrointestinal stromal tumors (GIST)

Leukemia is a type of blood cancer and usually starts in white blood cells. Leukemia can be fast-growing (acute) or more slow-growing (chronic).

Some types of leukemias are known as Philadelphia positive (Ph+). The BCR-ABL fusion gene (Philadelphia chromosome) is usually found in patients with chronic myelogenous leukemia (CML), and in some patients with acute lymphoblastic leukemia (ALL).

The Philadelphia chromosome occurs when a piece of chromosome 9 and a piece of chromosome 22 break off and trade places. The BCR-ABL gene is formed on chromosome 22 where the piece of chromosome 9 attaches. The changed chromosome 22 is called the Philadelphia chromosome.

• In chronic myeloid (or myelogenous) leukemia (CML), an abnormal gene called BCR-ABL changes the growth of early growth myeloid cells that lead to red blood cells, platelets and most types of white blood cells. These cells grow into leukemia cells, build up in the bone marrow, and move into the blood and spleen.
• Acute lymphocytic (or lymphoblastic) leukemia (ALL) starts in the bone marrow where new blood cells are made, but usually quickly moves into the blood. This leukemia may spread to other areas in the body like the lymph nodes, liver, or brain.

Myelodysplastic / myeloproliferative diseases (MDS/MPD) are a group of disorders in the blood and bone marrow.

• In this condition, the bone marrow makes too many blood cells, such as white blood cells, platelets, fibroblasts, and red blood cells.
• Gleevec is used in patients with MDS/MPD associated with PDGFR (platelet-derived growth factor receptor) gene rearrangements. Your doctor will determine PDGFRb gene rearrangements status prior to initiating treatment.

In aggressive systemic mastocytosis there is an elevated number of mast cells within the skin, bone marrow and organs such as liver, spleen, lymph nodes and gastrointestinal tract. A mast cell is a type of white blood cell that is found in connective tissues.

• Symptoms can include skin reactions, swollen spleen, liver or lymph nodes and stomach effects such as diarrhea, nausea or vomiting.
• The severity of systemic mastocytosis can range from mild to life-threatening depending upon where the disease occurs in the body.
• For this condition, Gleevec is used in patients without the D816V c-KIT mutation as determined with an FDA-approved test or if the c-KIT mutational status is unknown. Your doctor will determine your D816V c-Kit mutation status prior to initiating treatment.

Dermatofibrosarcoma protuberans (DFSP) is a skin cancer that is slow growing. It may appear as firm nodules that are dark, red-blue or flesh colored.

• Lumps may occur in the chest, stomach area, or leg, but usually do not usually spread within the body. Surgery to remove the tumors is usually successful, but in about half of cases the tumors may grow back, too.
• For this condition, Gleevec targets the PDGFR protein.

Hypereosinophilic syndrome (HES) and chronic eosinophilic leukemia (CEL) lead to the growth of too many eosinophils, a type of white blood cell, which can lead to organ damage.

• Gleevec is used for adult patients with HES/CEL who have FIP1L1-PDGFRα fusion kinase (mutational analysis or fluorescence in situ hybridization [FISH] demonstration of CHIC2 allele deletion), and for patients with HES and/or CEL who are FIP1L1-PDGFRα fusion kinase negative or unknown.

KIT+ gastrointestinal stromal tumors (GISTs) are soft tissue sarcomas (cancers that begin in the bones and the soft tissues ).

• GISTs can be located in any part of the digestive system. Their most common sites are the stomach and small intestine.
• Gleevec is approved to be used in patients with KIT (CD117)-positive unresectable (cannot be removed by surgery) and/or metastatic (spread within the body) malignant gastrointestinal stromal tumors (GIST) and as a treatment of adult patients following complete surgical removal of a KIT (CD117)-positive GIST.

This is not all the information you need to know about Gleevec (imatinib) for safe and effective use and does not take the place of talking to your doctor about your treatment. Review the full product information and discuss this information and any questions you have with your doctor or other health care provider.

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