The U.S. Food and Drug Administration (FDA) expanded the approval of Rituxan® (rituximab) to include maintenance therapy for patients with advanced follicular lymphoma that has responded to initial treatment with Rituxan and chemotherapy.
Rituxan is a targeted therapy that binds to a marker known as CD20 on the surface of B-cells. This binding prompts the immune system to destroy the cell, and also has direct anticancer effects on the cell. Rituxan is commonly used in the treatment of B-cell non-Hodgkin’s lymphomas (NHL) and chronic lymphocytic leukemia (CLL).
Maintenance therapy refers to longer-term treatment that is given after patients achieve remission with standard therapy. The goal of maintenance therapy is to prolong remission.
Rituxan Approved as Maintenance Therapy for Follicular Lymphoma
Rituxan maintenance therapy was evaluated in a Phase III clinical trial known as PRIMA. The study enrolled primarily patients with Stage III or IV follicular lymphoma whose disease had been reduced or eliminated by initial treatment with a combination of chemotherapy and Rituxan. Half the study participants were assigned to receive an additional two years of Rituxan as maintenance therapy and half received no maintenance therapy. These results were published in the The Lancet.
Patients were followed for a median of three years.
- Three-year progression-free survival was 74.9% among patients given Rituxan maintenance therapy compared with 57.6% of patients given no maintenance therapy.
- Overall survival did not differ significantly between the two groups.
- Patients in the Rituxan maintenance group were more likely to experience infections (39% versus 24% in the no-maintenance group).
- Quality of life was similar in the two study groups.
These results suggest that maintenance therapy with Rituxan prolongs remission among patients with follicular lymphoma.
Maintenance Rituxan® Improves Outcomes for Relapsed/Refractory Follicular and Mantle Cell Non-Hodgkin’s Lymphoma
According to results presented at the 42nd annual meeting of the American Society of Clinical Oncology (ASCO), additional therapy with Rituxan® following initial therapy with fludarabine/cyclophosphamide/miktoxantrone/Rituxan (R-FCM) lengthens anticancer responses in patients with relapsed or refractory follicular or mantle cell lymphoma. As well, there is a trend toward improved overall survival with R-FCM in these patients.
Researchers affiliated with the German Low Grade Lymphoma Study Group (GLSG) presented final analysis of a trial that evaluated the use of maintenance Rituxan following induction with R-FCM in relapsed or refractory follicular or mantle cell lymphoma. Patients either received initial therapy with R-FCM with no follow-up treatment (observation group) or were treated with R-FCM followed by maintenance Rituxan.
- At three years, survival rates were 82% in the group treated with maintenance Rituxan and 55% for those in the observation group.
- Both treatment groups experienced first severe infections around the same time.
The researchers concluded that maintenance Rituxan for the treatment of relapsed/refractory follicular lymphoma or mantle cell lymphoma following induction R-FCM significantly improves progression-free survival with trend toward improved overall survival compared to observation.
Rituxan® as Maintenance Therapy Reduces Relapses in Non-Hodgkin’s Lymphoma
Results from a recent phase III clinical trial indicate that maintenance therapy with Rituxan® improves progression-free survival in patients with NHL. The results of this trial were so promising that the trial was stopped early.
Researchers associated withv EORTC conducted a phase III clinical trial that included 18 countries to evaluate maintenance therapy with Rituxan in patients with NHL.
This trial included 465 patients with recurrent indolent NHL. Patients were initially treated with Rituxan plus the chemotherapy regimen referred to as CHOP or with CHOP alone. Overall, results (which have been reported previously) indicated that patients treated with Rituxan/CHOP had better progression-free survival than those treated with CHOP alone.
The next part of the trial involved evaluating the effectiveness of two years of Rituxan as maintenance therapy compared to placebo (inactive substitute) in these patients. Their initial treatment included Rituxan/CHOP or CHOP alone.
At approximately 18 months follow-up, both groups of patients (those treated initially with Rituxan/CHOP and those treated only with CHOP) experienced an improvement in progression-free survival when treated with maintenance Rituxan compared to placebo.
Treanda® and Rituxan® Effective for Relapsed CLL
In a Phase II clinical trial, the combination of Treanda® (bendamustine)®and Rituxan® produced promising results among patients with relapsed CLL.
CLL is the most common adult leukemia, with over 15,000 individuals diagnosed per year in the United States and more than 4,000 deaths. CLL is a disease characterized by high numbers of circulating abnormal lymphocytes (B-cells) in the peripheral blood. The disease often involves enlargement of lymph nodes in various parts of the body as well as enlargement of the spleen. It typically occurs in individuals between 65 and 70 years of age.
Treanda is a chemotherapy agent that has been approved for the treatment of CLL and certain types of non-Hodgkin®s lymphoma.
To evaluate the combination of Treanda and Rituxan in the treatment of CLL, researchers in Germany conducted a Phase II clinical trial among 81 patients with relapsed or refractory CLL (CLL that had returned after prior treatment, or that was resistant to prior treatment). All patients were treated with both drugs.
- 77% of patients experienced a complete or partial disappearance of detectable cancer following treatment:
- 63% of patients had a partial response.
- 14% of patients had a complete response.
- Severe side effects included low blood counts and infection.
These results suggest that the combination of Treanda and Rituxan is active against relapsed or refractory CLL. These results have led to a new trial comparing the efficacy of Treanda and Rituxan to Fludara® (fludarabine), Cytoxan® (cyclophosphamide) and Rituxan for treatment of newly diagnosed patients.
- Friedberg JW. Rituximab maintenance in follicular lymphoma: PRIMA. The Lancet [early online publication]. December 21, 2010.
- Genentech news release. FDA approves Rituxan for first-line maintenance use in follicular lymphoma. January 28, 2011.
- Fischer K, Stilgenbauer S, Schweighofer CD et al. Bendamustine in combination with rituximab (BR) for patients with relapsed chronic lymphocytic leukemia (CLL): a multicentre phase II trial of the German CLL Study Group (GCLLSG). Presented at the 50th Annual Meeting of the American Society of Hematology, San Francisco, CA, December 6-9, 2008. Abstract 330.
- Roche. Phase III MabThera maintenance trial in lymphoma shows positive results earlier than expected. Available at: . Accessed October 2005
- Dreyling M, Forstpointer R, Gramatzki M, et al. Rituximab Maintenance Improves Progression-Free and Overall Survial Rates after Combined Immuno-Chemotherapy (R-FCM) I Patients with Relapsed Follicular and Mantle Cell Lymphoma: Final Results of a Prospective Randomized Trial of the German Low Grade Lymphoma Study Group (GLSG). Proceedings from the 42nd annual meeting of the American Society of Clinical Oncology. Atlanta, GA. June 2006. Abstract # 7502
- Salles G, Seymour JF, Offner F et al. Rituximab maintenance for 2 years in patients with high tumour burden follicular lymphoma responding to rituximab plus chemotherapy (PRIMA): a phase 3, randomised controlled trial. The Lancet [early online publication]. December 21, 2010.