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Key Words

Non-Hodgkin's lymphoma, B-cell lymphoma, elderly, targeted therapy, rituximab (Rituxan®). (Definitions of many terms related to cancer can be found in the Cancer.gov Dictionary ³.)

Summary

Elderly patients with B-cell lymphoma stayed disease-free for significantly longer when they were treated with the drug rituximab. Patients benefited from rituximab whether they got it with their initial standard chemotherapy or as maintenance therapy afterward. These findings establish a new standard of care for the treatment of elderly patients with B-cell lymphoma.

Source

Journal of Clinical Oncology, published online June 5, 2006; in print July 1, 2006 (see the journal article).
(J Clin Oncol. 2006 Jul 1;24(19):3121-7. Epub 2006 Jun 5)

Background

B-cell lymphoma is a cancer of the B cells, a type of white blood cell. As part of the immune system, normal B cells make antibodies and help fight infections. B-cell lymphoma is the most common type of non-Hodgkin's lymphoma. More than 60 percent of patients are over age 60 when they are diagnosed with B-cell lymphoma.

For the past 30 years the chemotherapy regimen of cyclophosphamide, doxorubicin, vincristine, and prednisone, known as CHOP, has been the standard therapy for B-cell lymphoma. Younger patients may benefit from high doses of chemotherapy combined with a stem-cell transplant, but this approach is considered too toxic for older patients.

Rituximab is a monoclonal antibody that binds to a specific protein (CD20) on the surface of many B cells, tagging those cells for destruction by the patient’s own immune system. Targeted therapies such as rituximab tend to be less toxic than other kinds of systemic treatments that affect a variety of normal tissues. Preliminary studies suggested that patients with B-cell lymphoma might benefit from the addition of rituximab to standard treatment with CHOP.

The Study

This phase III study involved 1,047 patients with B-cell lymphoma whose median age was 69, and was conducted between February 1998 and July 2001. The patients were randomly assigned to initial (or induction) treatment with either CHOP plus rituximab (R-CHOP) or CHOP alone. After completing their assigned treatment, patients whose tumors had disappeared or shrank significantly were once more randomly assigned

The study was conducted by researchers with the Eastern Cooperative Oncology Group, the Cancer and Leukemia Group B, and the Southwest Oncology Group, three of nine research groups supported by the National Cancer Institute (NCI) to conduct large, multicenter cancer trials. The principal investigator was Thomas M. Habermann, M.D., of the Mayo Clinic in Rochester, Minnesota.

Results

At a median follow-up point of three and a half years, 53 percent of patients who received R-CHOP after the first randomization were alive without having had a relapse of their disease (called failure-free survival). By contrast, 46 percent of patients treated with CHOP alone remained alive without relapse. These results were statistically significant. Overall survival rates, however, were not significantly different. Side effects were similar between the two groups.

Among patients who were randomized a second time, 76 percent of those treated with maintenance rituximab were alive and disease-free after two years, compared with 61 percent of those in the observation group, findings that were statistically significant. Again, however, there was no difference in terms of overall survival.

In the group of patients who were initially treated with CHOP alone, 74 percent of those who went on to receive maintenance rituximab remained alive and free of disease after two years, compared with 49 percent of those who were merely observed. Notably, however, patients who received rituximab as part of both induction (R-CHOP) and maintenance therapy didn’t fare any better than those who were merely observed after their R-CHOP induction. In other words, for R-CHOP patients, maintenance rituximab provided no additional benefit.

Comments

“We recommend R-CHOP as the standard treatment for older [patients with B-cell lymphoma],” the study authors write.

Michael Bishop, M.D., of the National Cancer Institute’s Center for Cancer Research, agrees. “R-CHOP has become the standard of care for older patients with B-cell lymphoma,” he says. “Giving rituximab as maintenance therapy on the basis of the patient’s response to induction therapy with CHOP could deny a potentially effective therapy to patients whose disease does not respond to CHOP alone.”

Limitations

This study was conducted in older patients and the results may not apply to younger people with B-cell lymphoma, notes Bishop.

Glossary Terms

A protein made by plasma cells (a type of white blood cell) in response to an antigen (a substance that causes the body to make a specific immune response). Each antibody can bind to only one specific antigen. The purpose of this binding is to help destroy the antigen. Some antibodies destroy antigens directly. Others make it easier for white blood cells to destroy the antigen.

A type of protein made in the laboratory that can locate and bind to substances in the body, including tumor cells. There are many kinds of monoclonal antibodies. Each monoclonal antibody is made to find one substance. Monoclonal antibodies are being used to treat some types of cancer and are being studied in the treatment of other types. They can be used alone or to carry drugs, toxins, or radioactive materials directly to a tumor.

A study to compare the results of people taking a new treatment with the results of people taking the standard treatment (for example, which group has better survival rates or fewer side effects). In most cases, studies move into phase III only after a treatment seems to work in phases I and II. Phase III trials may include hundreds of people.

A study in which the participants are assigned by chance to separate groups that compare different treatments; neither the researchers nor the participants can choose which group. Using chance to assign people to groups means that the groups will be similar and that the treatments they receive can be compared objectively. At the time of the trial, it is not known which treatment is best. It is the patient's choice to be in a randomized trial.

A monoclonal antibody used to treat certain types of B-cell non-Hodgkin lymphoma and symptoms of rheumatoid arthritis. Monoclonal antibodies are made in the laboratory and can bind to substances in the body, including cancer cells. Rituximab binds to the protein called CD20, which is found on B-cells, and may kill cancer cells. Also called Rituxan.

In medicine, treatment that experts agree is appropriate, accepted, and widely used. Health care providers are obligated to provide patients with the standard of care. Also called best practice and standard therapy.

Describes a mathematical measure of difference between groups. The difference is said to be statistically significant if it is greater than what might be expected to happen by chance alone. Also called significant.

A method of replacing immature blood-forming cells that were destroyed by cancer treatment. The stem cells are given to the person after treatment to help the bone marrow recover and continue producing healthy blood cells.

A type of treatment that uses drugs or other substances, such as monoclonal antibodies, to identify and attack specific cancer cells. Targeted therapy may have fewer side effects than other types of cancer treatments.

A type of immune cell. Most white blood cells are made in the bone marrow and are found in the blood and lymph tissue. White blood cells help the body fight infections and other diseases. Granulocytes, monocytes, and lymphocytes are white blood cells. Also called leukocyte and WBC.