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Key words

Summary

In a pooled analysis of data from five clinical trials in patients with follicular lymphoma whose disease had relapsed or was resistant to treatment, those who received maintenance therapy with rituximab survived longer than those who did not receive maintenance therapy. However, this finding leaves unanswered the question of whether maintenance rituximab is superior to treatment with rituximab on relapse.

Source

Journal of the National Cancer Institute, February 18, 2009 (see the journal abstract ⁴).

Background

Follicular lymphoma is one of the most common kinds of non-Hodgkin lymphoma. Although the progression rate varies widely, follicular lymphoma typically progresses slowly and causes few symptoms. Patients with follicular lymphoma usually survive for at least 10 years after diagnosis.

Rituximab (Rituxan®) is a monoclonal antibody that has been used to treat various cancers of the blood (leukemia) and the lymphatic system (lymphoma). It has been used successfully, both alone and in combination with standard chemotherapy, in patients whose follicular lymphoma has recurred or proven resistant to other treatment. The addition of rituximab to first-line chemotherapy has been found to improve survival of patients with previously untreated follicular lymphoma.

Maintenance therapy is treatment given to patients who have responded to initial, or induction, therapy to help keep their cancer in remission. The value of rituximab as maintenance therapy for patients with follicular lymphoma has been unclear.

The Study

The five trials involved a total of 1,143 adult patients with indolent, or slow-growing, lymphoma. Most of the patients had follicular lymphoma, and most had disease that had relapsed or was not responding to treatment (refractory). The trials were conducted between 1998 and 2004; two were conducted in the United States and the others were conducted in Europe and elsewhere.

Patients who had been randomly assigned to rituximab maintenance therapy received either a single infusion every two to three months or four weekly infusions every six months for two years. The median follow-up period ranged from a little over two years to about three and a half years. The study's principal investigator was Liat Vidal, M.D., of Rabin Medical Center in Israel.

Results

Survival data were available for 985 patients with follicular lymphoma. In the pooled analysis of all five trials, patients who were treated with rituximab maintenance therapy had better overall survival than those who did not. The trials were also analyzed separately according to the type of control group (that is, whether or not rituximab was given at relapse to patients who had not received maintenance rituximab). Among patients in the four trials in which the control group did not receive rituximab at relapse, patients who received rituximab maintenance lived significantly longer than those who did not. Among patients in the single trial in which the control group did receive rituximab at relapse, survival was not improved in those who received rituximab maintenance treatment. However, this trial was too small to show whether one treatment approach was superior to the other.

In the overall analysis, a survival benefit of maintenance rituximab appeared to be restricted to patients with previously treated (that is, refractory or relapsed) follicular lymphoma; no such benefit was seen in patients who had not received previous treatment for follicular lymphoma.

Patients treated with rituximab maintenance therapy developed more severe infections and other adverse effects than patients in the control group.

Limitations

The five studies used a variety of induction therapy regimens--chemotherapy alone (one trial), rituximab alone (two trials), and chemotherapy with or without rituximab (one trial). The use of different induction regimens could have reduced the comparability of the trials. In addition, three of the five trials were stopped earlier than initially planned, which could have inflated the estimates of treatment benefit. Finally, only one of the trials compared maintenance rituximab with rituximab given at relapse.

Comment

This analysis confirms the value of rituximab in extending the lives of patients with follicular lymphoma, says Wyndham Wilson, M.D., head of the Lymphoma Therapeutics Section of the National Cancer Institute's Center for Cancer Research. However, he adds, it does not answer the question of whether patients treated with maintenance rituximab live longer than patients who receive rituximab when their disease relapses.

"We know that patients with follicular lymphoma benefit from treatment with rituximab," says Wilson. "But we cannot conclude from this analysis that maintenance therapy is the optimal approach to administering rituximab."

The current standard of care in the United States is to treat patients with follicular lymphoma with rituximab when their disease relapses after initial chemotherapy, notes Wilson. The findings of this analysis do not justify changing that standard, he concludes.

Glossary Terms

An unexpected medical problem that happens during treatment with a drug or other therapy. Adverse effects do not have to be caused by the drug or therapy, and they may be mild, moderate, or severe. Also called adverse event.

Treatment with drugs that kill cancer cells.

A type of research study that tests how well new medical approaches work in people. These studies test new methods of screening, prevention, diagnosis, or treatment of a disease. Also called clinical study.

In a clinical trial, the group that does not receive the new treatment being studied. This group is compared to the group that receives the new treatment, to see if the new treatment works.

A clinical study that includes a comparison (control) group. The comparison group receives a placebo, another treatment, or no treatment at all.

The process of identifying a disease, such as cancer, from its signs and symptoms.

A type of B-cell non-Hodgkin lymphoma (cancer of the immune system) that is usually indolent (slow-growing). The tumor cells grow as groups to form nodules. There are several subtypes of follicular lymphoma.

Monitoring a person's health over time after treatment. This includes keeping track of the health of people who participate in a clinical study or clinical trial for a period of time, both during the study and after the study ends.

A type of cancer that grows slowly.

Initial treatment used to reduce a cancer. Induction therapy is followed by other treatments, such as chemotherapy, radiation therapy, and hormone therapy to get rid of cancer that remains. Also called first-line therapy, primary therapy, and primary treatment.

Invasion and multiplication of germs in the body. Infections can occur in any part of the body and can spread throughout the body. The germs may be bacteria, viruses, yeast, or fungi. They can cause a fever and other problems, depending on where the infection occurs. When the body’s natural defense system is strong, it can often fight the germs and prevent infection. Some cancer treatments can weaken the natural defense system.

A method of putting fluids, including drugs, into the bloodstream. Also called intravenous infusion.

Cancer that starts in blood-forming tissue such as the bone marrow and causes large numbers of blood cells to be produced and enter the bloodstream.

The tissues and organs that produce, store, and carry white blood cells that fight infections and other diseases. This system includes the bone marrow, spleen, thymus, lymph nodes, and lymphatic vessels (a network of thin tubes that carry lymph and white blood cells). Lymphatic vessels branch, like blood vessels, into all the tissues of the body.

Cancer that begins in cells of the immune system. There are two basic categories of lymphomas. One kind is Hodgkin lymphoma, which is marked by the presence of a type of cell called the Reed-Sternberg cell. The other category is non-Hodgkin lymphomas, which includes a large, diverse group of cancers of immune system cells. Non-Hodgkin lymphomas can be further divided into cancers that have an indolent (slow-growing) course and those that have an aggressive (fast-growing) course. These subtypes behave and respond to treatment differently. Both Hodgkin and non-Hodgkin lymphomas can occur in children and adults, and prognosis and treatment depend on the stage and the type of cancer.

Treatment that is given to help keep cancer from coming back after it has disappeared following the initial therapy. It may include treatment with drugs, vaccines, or antibodies that kill cancer cells, and it may be given for a long time.

A statistics term. The middle value in a set of measurements.

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.

Any of a large group of cancers of lymphocytes (white blood cells). Non-Hodgkin lymphomas can occur at any age and are often marked by lymph nodes that are larger than normal, fever, and weight loss. There are many different types of non-Hodgkin lymphoma. These types can be divided into aggressive (fast-growing) and indolent (slow-growing) types, and they can be formed from either B-cells or T-cells. B-cell non-Hodgkin lymphomas include Burkitt lymphoma, chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), diffuse large B-cell lymphoma, follicular lymphoma, immunoblastic large cell lymphoma, precursor B-lymphoblastic lymphoma, and mantle cell lymphoma. T-cell non-Hodgkin lymphomas include mycosis fungoides, anaplastic large cell lymphoma, and precursor T-lymphoblastic lymphoma. Lymphomas that occur after bone marrow or stem cell transplantation are usually B-cell non-Hodgkin lymphomas. Prognosis and treatment depend on the stage and type of disease. Also called NHL.

In medicine, the course of a disease, such as cancer, as it becomes worse or spreads in the body.

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.

To come back or to return.

In medicine, describes a disease or condition that does not respond to treatment.

A treatment plan that specifies the dosage, the schedule, and the duration of treatment.

The return of signs and symptoms of cancer after a period of improvement.

A decrease in or disappearance of signs and symptoms of cancer. In partial remission, some, but not all, signs and symptoms of cancer have disappeared. In complete remission, all signs and symptoms of cancer have disappeared, although cancer still may be in the body.

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. Rituxan binds to the protein called CD20, which is found on B-cells, and may kill cancer cells. Also called rituximab.

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.