Gleevec (imatinib) is a cancer medication approved to treat seven different conditions, most notably chronic myeloid leukemia (CML) and gastrointestinal stromal tumors (GIST). It was one of the first targeted cancer therapies, designed to block specific proteins that drive cancer cell growth rather than killing cells indiscriminately like traditional chemotherapy. Since its FDA approval in 2001, it has transformed CML from a near-certain death sentence into a manageable chronic disease, with 10-year survival rates around 77%.
How Gleevec Works
Most cancers Gleevec treats share a common feature: they’re driven by overactive signaling proteins called kinases. In CML, a genetic accident fuses two genes together, creating an abnormal protein called BCR-ABL. This protein acts like a stuck “on” switch, telling white blood cells to multiply uncontrollably. Gleevec fits into the protein’s energy-receiving pocket and locks it into an inactive shape, effectively flipping the switch off. Without that signal, the leukemia cells stop growing and die.
The same principle applies to GIST and the drug’s other approved uses. Different cancers rely on different kinases, but Gleevec happens to block several of them, including the ones driving gastrointestinal stromal tumors (called KIT) and certain rare blood disorders (driven by a growth factor receptor called PDGFR). This multi-target activity is why one drug can treat such a diverse set of diseases.
Chronic Myeloid Leukemia
CML is Gleevec’s primary and best-known use. It’s approved for both newly diagnosed adults and children with Philadelphia chromosome-positive CML in the chronic phase, the earliest and most treatable stage. It’s also used for patients in more advanced stages (accelerated phase or blast crisis) and for those whose disease didn’t respond to older treatments.
Before Gleevec, the five-year survival rate for CML was roughly 30%. A real-world study tracking patients over a decade found that 77.8% of those who started on Gleevec as their first treatment were alive at 10 years. That shift is one of the most dramatic in modern oncology. Most patients take the drug as a daily pill and continue for years, often indefinitely, with regular blood tests to track how well the leukemia is responding.
Doctors monitor CML patients closely during the first year, checking blood and bone marrow samples every three months to measure how much of the BCR-ABL gene signal remains. A key early benchmark comes at three months: patients whose leukemia gene levels drop below 1% of a reference value have only about a 4% risk of the disease progressing. Those with higher levels at that point may need a treatment change. By 12 months, the goal is a complete cytogenetic response, meaning no detectable Philadelphia chromosome-positive cells in the bone marrow.
Gastrointestinal Stromal Tumors
GIST is a type of cancer that forms in the wall of the digestive tract, most commonly the stomach or small intestine. Gleevec is approved for GIST tumors that can’t be surgically removed or have spread to other parts of the body, and also as a follow-up treatment after surgery to reduce the chance of recurrence.
The standard starting dose for GIST is 400 mg daily, and more than 80% of patients with advanced disease respond to this dose. For patients with a specific genetic subtype (KIT exon 9 mutation), a higher dose of 800 mg daily tends to work better. If a tumor starts growing again on the standard dose, increasing to 800 mg can stabilize or shrink the disease in roughly one-third of patients.
Other Approved Uses
Beyond CML and GIST, Gleevec is approved for several less common conditions:
- Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL): A fast-growing leukemia in both adults (whose disease has returned or hasn’t responded to other treatment) and newly diagnosed children (combined with chemotherapy).
- Myelodysplastic/myeloproliferative diseases (MDS/MPD): A group of rare bone marrow disorders where blood cells don’t develop normally. Gleevec works specifically in cases driven by PDGFR gene rearrangements.
- Aggressive systemic mastocytosis: A condition where abnormal mast cells (immune cells involved in allergic reactions) accumulate in organs. Gleevec is used when the cancer cells lack a particular mutation (D816V) that would make them resistant to the drug.
- Hypereosinophilic syndrome (HES) and chronic eosinophilic leukemia: Conditions involving dangerously high levels of a type of white blood cell called eosinophils. In early studies, patients with HES achieved complete remission on Gleevec at doses ranging from 100 to 400 mg daily.
- Dermatofibrosarcoma protuberans (DFSP): A rare, slow-growing skin cancer. Gleevec is used when the tumor can’t be fully removed by surgery or has come back.
Common Side Effects
Gleevec’s side effects are well documented across thousands of patients in clinical trials. The most frequent issue is fluid retention, particularly swelling around the eyes, hands, and feet, which affects about 60% of CML patients and up to 77% of GIST patients. This is usually mild and manageable but should be monitored.
Other common side effects in CML trials included nausea (50%), muscle cramps (49%), muscle and bone pain (47%), diarrhea (45%), skin rash (40%), fatigue (39%), and headache (37%). GIST patients reported similar issues at somewhat higher rates, with fatigue affecting nearly 70% and nausea about 58%. Most of these side effects are mild to moderate and tend to be most noticeable in the first few months of treatment.
When Gleevec Stops Working
Some patients develop resistance to Gleevec over time, most often because the cancer cells acquire new genetic mutations that change the shape of the protein Gleevec targets. The drug can no longer fit into the binding pocket, and the cancer starts growing again. Mutations in the BCR-ABL gene’s kinase domain are the most common cause of relapse in CML patients. A handful of specific mutations account for the majority of resistance cases, with changes at positions 315, 253, 255, and 351 in the protein identified in about 60% of patients who relapse with detectable mutations.
One mutation in particular, known as T315I, is especially problematic because it almost completely blocks Gleevec from binding. Newer drugs have been developed specifically to overcome this and other resistance mutations, giving patients additional options if Gleevec stops controlling their disease. When resistance develops, doctors typically test for these mutations to guide the choice of a second-line treatment.