Strategies to Improve Treatment - Chronic Phase

Much progress has been made in the treatment of chronic phase chronic myeloid leukemia (CML), but better treatment strategies are still needed. Future progress in the treatment of leukemia will result from continued participation in appropriate clinical studies. There are several areas of research aimed at improving the treatment of leukemia.

Treatment with Gleevec^® (imatinib mesylate) - Imatinib mesylate may be the most exciting treatment for CML ever developed. Imatinib mesylate appears to be capable of producing complete cytogenetic remissions in 80 percent of patients. It is unknown if some of these patients who achieve a complete molecular response will be cured. It is now the best front-line treatment of CML. With imatinib mesylate, more than 90 percent of patients are alive 5 years into the treatment.

New Tyrosine Kinase Inhibitors

1. Sprycel^® (dasatinib; BMS354825) - This is a dual Src-Abl inhibitor, 300 times more potent than imatinib. It is capable of producing hematologic responses in 90 percent of patients in chronic phase CML after failure of imatinib, and suppressed the Ph-positive cells in 50 percent of patients. It is now approved by the FDA for the treatment of CML in all phases after progression or intolerance to imatinib.

2. Tasigna (nilotinib; AMN107) - This is also a selective potent Bcr-Abl inhibitor, 30 to 50 times more potent than imatinib. Like dasatinib, nilotinib is also very active in the clinic after imatinib failure. It is expected to be approved by the FDA next year.

3. Other tyrosine kinase inhibitors - There are many including SKI606, INNO406, and others. Trials with these drugs are available and you may wish to ask your doctor about whether you may benefit from them.

Other targeted therapies - A class of drugs called aurora kinase inhibitors may also be active in CML, particularly in patients with one particular resistant mutation to the above drugs—called T315I. These include drugs like MK0457, AT9283, KW2449, and others.

Other programs - The combination of cytarabine and interferon is a reasonable treatment option for patients unable to pursue imatinib or curative treatment with allogeneic stem cell transplantation.

A new drug called homoharringtonine is designed to reduce the number of leukemia cells. Patients who received homoharringtonine experienced a higher complete hematologic remission rate and a higher cytogenetic remission rate (disappearance of the Philadelphia chromosome) compared with patients who only received interferon. The patients in the homoharringtonine group also needed less interferon to stay in remission. Current and future studies will address the best way to combine this and other drugs like imatinib.

Monitoring of treatment - After treatment of CML, doctors often use a bone marrow aspiration procedure to test the bone marrow cells to identify whether the leukemia cells with the abnormal Philadelphia chromosome are gone and to determine how well the treatment is working.

While the bone marrow test is useful, it also has some disadvantages. The bone marrow aspiration may be painful or uncomfortable. For these reasons, researchers continue to develop and study the use of less invasive, more sensitive tests to detect the Philadelphia chromosome and monitor the effectiveness of treatment through peripheral blood studies.

A new test, fluorescence in situ hybridization (FISH), detects the Philadelphia chromosome in the blood, rather than the bone marrow, of people with CML who had undergone treatment. The FISH test was as sensitive as bone marrow aspiration in detecting the Philadelphia chromosome in the blood and helping to determine the treatment outcomes for these patients.

The FISH test may be used to determine the treatment outcomes for individuals with CML without use of a bone marrow examination. However, the FISH test may not be used exclusively; those who test negative for the Philadelphia chromosome will need a follow-up with a more sensitive test—called a polymerase chain reaction (PCR). The FISH test appears to be an improved method for the routine monitoring of treatment outcomes in people with CML. You may wish to talk with your doctor about the advantages and disadvantages of FISH and PCR testing and other blood tests in determining the effectiveness of your treatment.