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Maintenance Rituximab May Improve Survival in Follicular Lymphoma

Key words

Rituximab (Rituxan®), follicular lymphoma, non-Hodgkin lymphoma, maintenance therapy


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.


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


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

An international group of researchers searched the published literature for randomized controlled trials that compared survival of patients who received rituximab maintenance therapy with that of patients who did not receive maintenance therapy (control patients). Five trials were identified, and the data were pooled for analysis. In one trial, patients in the control group were given rituximab when their disease relapsed; in the other four trials, treatment at relapse in the control arm was not part of the studies and no information was provided on the use of subsequent rituximab.

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.


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.


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.


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.

  • Posted: April 2, 2009