According to results recently presented at the 47th annual American Society of Hematology (ASH) meeting, a novel agent desatinib (BM-354825), which is still in clinical trials, is an effective treatment option for patients with chronic myelogenous leukemia (CML) who do not respond to Gleevec (imatinib mesylate).
Chronic myeloid leukemia (CML), also called chronic granulocytic leukemia, is a cancer that originates in the immune cells. It affects approximately 4,600 people annually in the U.S. In the case of CML, large numbers of young immune cells do not mature, resulting in an excess accumulation of these cells. These leukemia cells then crowd the bone marrow and blood, suppressing formation and function of other blood cells normally present in these areas. In addition, the leukemia cells cannot perform their function in the body properly, leaving patients susceptible to infection.
Chronic myeloid leukemia begins with a chronic phase, during which few clinical problems, if any, occur. However, when left untreated, the chronic phase progresses into acute phases; these phases are characterized by fast-growing and aggressive cancer and are called the accelerated and blastic phases. Patients reaching these acute phases have a poor prognosis for long-term survival.
Historically, the only curative option for patients with CML was an allogeneic stem cell transplant. However, treatment-related mortality, as well as side effects, can be substantial in patients undergoing an allogeneic stem cell transplant; researchers have thus focused efforts on curative treatment options that are more easily tolerated.
Philadelphia chromosome-positive CML refers to the majority of cases of CML in which a genetic abnormality, referred to as the Philadelphia chromosome, results in constantly activated growth of cancer cells. Gleevec is a biological agent that binds to and slows or stops the uncontrolled growth of cancer cells with this genetic mutation. In addition, Gleevec has activity in several biological pathways implicated in the development and/or expression of cancer. Gleevec is approved by the FDA for the treatment of adult and pediatric patients with CML and has become a standard treatment option. Unfortunately, a small number of patients who are treated with Gleevec do not achieve anticancer responses; researchers are evaluating novel agents for this group of patients.
Researchers recently conducted a clinical trial to evaluate the novel agent desatinib in patients with CML. This trial, referred to as the START trial, included patients with chronic-phase CML, accelerated-phase CML, and blastic-phase CML who either did not respond to Gleevec or could not tolerate Gleevec. Desatinib provided significant anticancer activity in these patients.
- Patients with chronic-phase CML had a complete hematologic remission rate (disappearance of leukemic cells in the blood) of 88%, and a major cytogenetic response (disappearance of cancerous genetic mutations) rate of 40%.
- Patients with accelerated-phase and blastic-phase CML had complete hematologic remission rates of 50%; however, approximately 80% in both groups achieved a major anticancer hematologic response.
- Patients with accelerated-phase and blastic-phase CML also experienced cytogenetic responses.
The researchers concluded that desatinib provides significant anticancer activity in patients with all phases of CML who are not responsive to Gleevec. Future trials will continue to evaluate desatinib in CML in order to provide long-term treatment outcomes utilizing this agent. Patients with CML who do not respond to Gleevec may wish to speak with their physician regarding their individual risks and benefits of participating in a clinical trial further evaluating desatinib or other promising novel therapeutic agents. Two sources of information regarding ongoing clinical trials include the National Cancer Institute (www.cancer.gov) and www.cancerconsultants.com.
Reference: Sayers CL, Kantarjian H, Shah J, et al. Dasatinib (BMS-354825) in patients with chronic myeloid leukemia (CML) and Philadelphia-Chromosome positive acute lymphoblastic leukemia (Ph+ ALL) who are resistant or intolerant to Gleevec. Proceedings from the 47th annual meeting of the American Society of Hematology. Blood. 2005;106:16a, abstract number 38
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