Gleevec® for CML: Long-lasting Anticancer Responses Confirmed

Cancer Connect

by Dr. C.H. Weaver M.D. updated 3/2020

Researchers from the Oregon Health and Science University have reported that patients with chronic-phase chronic myeloid leukemia (CML) experience long-term, durable anticancer responses to first-line treatment with Gleevec® (imatinib mesylate). In fact, five-year overall survival with Gleevec is greater than with any other therapy for CML; as well, patients experience a diminishing annual frequency of disease progression while on the drug. These results, presented at the 42nd annual meeting of the American Society of Clinical Oncology (ASCO), confirm the use of Gleevec as standard initial therapy for patients with chronic-phase CML.

Chronic myeloid leukemia is the abnormal growth of white blood cells. The disease is associated with a chromosomal abnormality concerning the Philadelphia chromosome and plays a role in the development of the disease.

Initially in chronic myeloid leukemia, there is a gradual increase in mature, abnormal myeloid cells in the bone marrow. These cells eventually spill into the blood and other organs, causing symptoms such as fatigue from anemia or an enlarged spleen. The increase in leukemic cell numbers occurs slowly at first and is referred to as the chronic phase, but these cells invariably begin to increase more rapidly and/or include fewer mature cells, resulting in the accelerated or blastic phase.

Gleevec is approved by the FDA for the treatment of adult and pediatric patients with CML. It has become a standard initial treatment option for this disease. However, long-term results from patients treated with Gleevec have not yet been published-these results are necessary as researchers try to understand the role of transplantation in this disease.

About Gleevec

The follow-up results presented at ASCO included data from the IRIS (International Randomized Study of Interferon versus STI571) trial, which began in 2000. The IRIS trial included over 1,100 patients with chronic-phase CML who had not received prior therapy. Patients were randomly selected to receive Gleevec (400 mg/daily) or interferon-alpha/cytosine arabinoside (the standard therapy at that time).

Of the 553 patients given Gleevec, 69% of patients remain on therapy after five years, 11% of patients receiving Gleevec withdrew from therapy due to either disease progression or lack of efficacy, and 5.8% withdrew due to either side effects or death not associated with CML.

The following results were reported:

  • Among patients who remain on therapy, 89.4% have survived five years or more.
  • 93% of surviving patients have not experienced disease progression to accelerated phase or blast crisis.
  • Patients who continue treatment with Gleevec tend to experience less disease progression.
  • At five years, 96% of patients who continued to receive Gleevec had a complete anticancer response.

According to an international panel has made recommendations concerning treatment for patients with newly diagnosed chronic myeloid leukemia with Gleevec® (imatinib mesylate).

Chronic myeloid leukemia (CML), also called chronic granulocytic leukemia, is a cancer that originates in the immune cells. In 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 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, called the accelerated and blastic phases, are characterized by fast-growing and aggressive cancer. Patients reaching these acute phases have a poor prognosis for long-term survival.

The majority of cases of CML are Philadelphia chromosome-positive (Ph-positive). In such cases a genetic abnormality, referred to as the Philadelphia chromosome, results in the constantly activated growth of cancer cells. Roughly 30% of adult patients with acute lymphoblastic leukemia (ALL) also have this genetic abnormality.

Gleevec, which is targeted against pathways associated with the Philadelphia chromosome, has become a standard treatment for Philadelphia chromosome-positive CML. Specific guidelines for the use of Gleevec in the treatment of CML have recently been compiled.

Recommendations for the treatment of CML were determined based on a review by an international panel of experts of literature concerning CML that had been written since 1998. The panel included 10 members from the European Union, one from Switzerland, seven from the United States, and one from Australia. They reviewed 194 papers. The following is a brief summary of this panel’s main conclusions:

  • All newly diagnosed patients should be treated with 400 mg of Gleevec per day.
  • Patients who either do not respond or do not respond adequately to Gleevec are advised to be treated with higher doses of Gleevec, an allogeneic stem cell transplantation, or experimental therapy (this may involve agents designed to overcome resistance to Gleevec).
  • It is very important for patients to speak with their physicians regarding the specific details of their responses to Gleevec. Responses to treatment are determined by several laboratory tests, and guidelines involving these responses have been defined.

Patients diagnosed with CML should speak with their physician regarding the latest guidelines for treatment and continued monitoring of their disease.

Gleevec has been confirmed as the standard, first-line treatment for patients with newly diagnosed chronic-phase CML, as the majority of patients have experienced long-term, durable responses. They state that younger patients with this disease may still benefit from an allogeneic stem cell transplant as up-front therapy. Long-term results will continue to be evaluated as these patients are followed. Patients with CML should discuss the potential risks and benefits of Gleevec therapy with their physician.

CML Patients Treated with Gleevec Have Normal Life Expectancy

People with chronic myeloid leukemia (CML) that is in complete remission after two years of treatment with Gleevec® (imatinib) have survival rates that are similar to those of the general population. These results were published in the Journal of the National Cancer Institute.

To explore the long-term outcomes of CML patients treated with Gleevec, researchers conducted a study among 832 patients in Europe, North and South America, Africa, the Middle East, and Asia. The study was restricted to patients who were in complete remission after two years of treatment with Gleevec.

  • 4.8% of patients died during follow-up, which is similar to what would be expected in a comparable group in the general population. Of the 20 deaths that occurred, only six were due to CML.
  • Common side effects included muscle cramps, weakness, swelling, skin fragility, diarrhea, and tendon or ligament problems. These side effects can affect quality of life, and patients are encouraged to discuss side effects with their physician.

A statement released by the journal notes that this study “offers the first evidence that a disseminated cancer, not amenable to surgery, can be controlled to the point of giving patients a normal life expectancy.” (3)

Pediatric CML

The United States Food and Drug Administration (FDA) has approved Gleevec® (imatinib mesylate) for the treatment of children with newly diagnosed chronic myelogenous leukemia.

Chronic myeloid leukemia (CML), also called chronic granulocytic leukemia, is a cancer that originates in the immune cells. In 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 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, called the accelerated and blastic phases, are characterized by fast-growing and aggressive cancer. Patients reaching these acute phases have a poor prognosis for long-term survival.

The majority of cases of CML are Philadelphia chromosome-positive (Ph-positive). In such cases a genetic abnormality, referred to as the Philadelphia chromosome, results in the constantly activated growth of cancer cells. Roughly 30% of adult patients with acute lymphoblastic leukemia (ALL) also have this genetic abnormality.

Gleevec, which is targeted against pathways associated with the Philadelphia chromosome, has become a standard treatment for Philadelphia chromosome-positive CML.

The clinical trial prompting approval of Gleevec for the treatment of children included 51 pediatric patients with newly diagnosed CML.

  • Blood cell levels were completely normal following treatment with Gleevec in 78% of patients.
  • Cytogenetics (relating to chromosome) abnormalities were completely normal in 65% of patients.

Trials including longer follow-up data will be conducted and will provide additional results for the use of Gleevec in pediatric patients with CML. Parents of children with CML may wish to speak with their physician regarding their individual risks and benefits of treatment with Gleevec. (4)

Reference:

  1. Druker B, Guilhot F, O’Brien S, et al. Long-Term Benefits of Imatinib (IM) for Patients Newly Diagnsoed with Chronic Myelogenous Leukemia in Chronic Phase (CML-CP): The 5-Year Update from the IRIS Study. Proceedings from the 42nd annual meeting of the American Society of Clinical Oncology. June 2006. Atlanta, GA. Abstract #6506.
  2. Baccarani M, Saglio G, Goldman J, et al. Evolving concepts in the management of chronic myeloid leukemia: recommendations from an expert panel on behalf of the European Net. Blood. 2006;108:1809-1820.
  3. Gambacorti-Passerini C, Antolini L, Mahon F-X et al. Multicenter independent assessment of outcomes in chronic myeloid leukemia patients treated with imatinib. Journal of the National Cancer Institute. Early online publication March 22, 2011.
  4. United States Food and Drug Administration. Gleevec package insert. Available at:www.fda.gov/cder/foi/label/2006/021588s016lbl.pdf. Accessed September 2006.

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