For most patients with chronic myelogenous leukemia (CML) in chronic phase, a drug called imatinib mesylate (trade name: Gleevec) is the standard first treatment. This page provides some details about imatinib as a treatment for CML. For a basic overview of CML and how it may be treated, see Chronic Myelogenous Leukemia, Imatinib and Transplant.
Measuring responses to imatinib
Patients with CML have an abnormal chromosome called the Philadelphia chromosome, which creates an abnormal gene called BCR/ABL. The BCR/ABL gene leads to the production of a type of enzyme called a tyrosine kinase, which signals the marrow to make too many white blood cells. Imatinib works by blocking the tyrosine kinase enzyme so that the marrow stops (or slows down) making too many white blood cells. For this reason, imatinib and similar drugs are called tyrosine kinase inhibitors, or TKIs.
Doctors measure how well imatinib is working by looking at a CML patient's blood and/or marrow cells. Based on these test results, doctors will say that a patient has either not responded, or has responded at one of these levels:
- Hematologic (blood) response — Blood counts have returned to normal.
- Cytogenetic (cellular) response — The number of cells with the Philadelphia chromosome has been reduced. A major cytogenetic response means at least 65% of cells are normal, and a complete cytogenetic response means all cells tested normal.
- Molecular response — When a very sensitive genetic test called PCR cannot detect any sign of the abnormal BCR/ABL genes that are created by the Philadelphia chromosome.
If even a small number of cells with the Philadelphia chromosome remain in the body, the patient could relapse (have the CML return). Therefore, the goal of treatment is to achieve a complete molecular response. However, even at this level of response, there can still be disease cells hidden in the body.
Results of clinical trials of imatinib
Starting in 2000, a large clinical trial was done to compare imatinib to interferon plus cytarabine — the best standard chemotherapy treatment at the time. [1, 2] The study included 1,106 patients with chronic phase CML who were assigned at random to be treated either with imatinib or with interferon combined with cytarabine. The estimated rates of response an average of 18 months after patients began treatment are shown in the table below.
|Type of Response
||Imatinib Response Rate
||Interferon + Cytarabine Response Rate
|Complete hematologic (blood) response
|Major cytogenetic (cellular) response
|Complete cytogenetic (cellular) response
|Major molecular response
||39% (after 12 months)
||2% (after 12 months)
|Disease did not get worse
In addition, patients taking imatinib had fewer side effects than those taking interferon together with cytarabine.  In a five-year update on this clinical trial published in 2006, researchers reported that most patients in this study still continue to do well on imatinib over the long term. 
However, if even a small number of cells with the Philadelphia chromosome remain in the body, the CML could return. One way doctors are trying to get rid of these cells is by giving higher doses of imatinib. In one clinical trial, 114 patients newly diagnosed with CML were given twice the usual dose of imatinib (400 mg twice a day).  This study found that at an average of 15 months after starting treatment:
- 63% of the patients showed a major molecular response
- None of the patients had their disease worsen to accelerated or blast phase
Exciting options for treating CML continue to be discovered. Two other TKIs have been developed: dasatinib (trade name: Sprycel®) and nilotinib (trade name: Tasigna®). These drugs have been shown to be very effective in the treatment of CML patients whose disease is resistant to imatinib. Additional clinical trials are now comparing these drugs to imatinib to determine if they can produce even higher responses in newly diagnosed CML patients.
Patients taking imatinib or the other TKIs are checked often to see if they are responding. Other treatments, either an allogeneic transplant or a change in drug therapy, are generally considered if such patients do not have:
- Complete hematologic remission at 3 months
- Evidence of cytogenetic remission at 6 months
- Major cytogenetic remission at 12 months
- Complete cytogenetic remission at 18 months
- Major molecular response at 18 months
Questions about imatinib
Because imatinib and other tyrosine kinase inhibitors are fairly new, there are still questions about them, including:
- How good does a patient's response need to be to control the disease? Many patients show only a partial response.
- How long will imatinib or other inhibitors control CML?
- Does imatinib or other inhibitors actually cure patients with CML? Most physicians believe that this is not the case.
- Can patients with no sign of disease eventually stop taking imatinib? This currently is not recommended as some patients have had their disease recur when they stopped imatinib even after obtaining molecular remission.
- What are the best treatment(s) for patients who do not respond to imatinib? Another CML drug, or an allogeneic transplant?
Imatinib does not work as well for patients in accelerated phase or blast phase. Also, some patients in chronic phase do not respond to imatinib or can lose their response over time (develop resistance). Doctors are looking for new ways to help these patients. Currently, for most patients, treatment with one of the newer tyrosine kinase inhibitors (dasatinib, nilotinib) is the next best option. Other options include pursuing a marrow, blood stem cell, or cord blood transplant, giving higher doses of imatinib, and combining imatinib with other drugs.
- O'Brien SG, Guilhot F, Larson RA, et al. Imatinib compared with interferon and low-dose cytarabine for newly diagnosed chronic-phase chronic myeloid leukemia. N Engl J Med. 2003; 348(11):994-1004.
- Druker BJ, Guilhot F, O'Brien SG, et al. Five-year follow-up of patients receiving imatinib for chronic myeloid leukemia. N Engl J Med. 2006; 355(23):2408-2417.
- Kantarjian H, Talpaz M, O'Brien S, et al. High-dose imatinib mesylate therapy in newly diagnosed Philadelphia chromosome-positive chronic phase chronic myeloid leukemia. Blood. 2004; 103(8):2873-2878.
Marcos de Lima, M.D., University of Texas M.D. Anderson Cancer Center, Houston, Texas
Richard T. Maziarz, M.D., Oregon Health and Science University, Portland, Ore.
Willis Navarro, M.D., National Marrow Donor Program, Minneapolis, Minn.