Rituximab Maintenance Therapy Boosts Survival in Tough-to-Treat Follicular Lymphoma
July 1, 2009
PETAH TIKVA, ISRAEL-Israeli investigators are recommending that maintenance therapy with rituximab be added to conventional therapy in patients with relapsed or refractory follicular lymphoma who have completed induction immunochemotherapy.
The recommendation comes from Dr Liat Vidal and colleagues at the Rabin Medical Center, following their meta-analysis of randomized controlled trials that compared rituximab maintenance therapy with observation or treatment at relapse in patients with follicular lymphoma.
The data showed that patients who were maintained on rituximab therapy were 40% more likely to remain alive at 3 years than patients assigned to observation or treatment at relapse.
The researchers reported their findings in the February 10, 2009, online issue of the Journal of the National Cancer Institute.
Follicular lymphoma has a high initial response rate however relapses are frequent, Vidal and associates noted in their article. While the monoclonal antibody rituximab in combination with chemotherapy has been shown to improve overall survival in patients with newly diagnosed and relapsed indolent lymphoma compared with chemotherapy alone, the drug's role as maintenance therapy in patients who responded to induction therapy has not been clarified, they said. Rituximab maintenance therapy for follicular lymphoma is not currently recommended in the National Comprehensive Cancer Network guidelines.
The meta-analysis included five trials enrolling a total of 1143 adult patients. Results in 985 evaluable patients demonstrated that rituximab maintenance therapy was associated with a 40% improvement in overall survival. The improvement in overall survival was significant in patients with relapsed or refractory disease; however, this same degree of benefit was not observed in previously untreated patients.
Patients receiving maintenance therapy had nearly twice as many infection-related adverse events, and these events were sometimes life-threatening.
Vidal and her associates pointed out that the study may have potential limitations. For example, three of the five trials included in the meta-analysis were stopped earlier than had been planned, which may result in an overestimation of treatment effects. In addition, the studies included in the meta-analysis used different types of induction therapy.
Several questions regarding the effect of rituximab maintenance on the outcome of patients with follicular lymphoma still need to be addressed, the authors wrote in their article. These questions include the effect of rituximab maintenance therapy versus rituximab at disease progression, the effects of rituximab maintenance therapy in previously untreated patients with advanced disease, and the effects of rituximab maintenance therapy after rituximab and chemotherapy induction. Research also needs to determine the optimal schedule and duration of rituximab maintenance as well as the drug's long-term toxicity.
For now, the Israeli group is recommending rituximab maintenance therapy for up to 2 years, either as four weekly infusions at 6-month intervals, or as a single infusion at 2- to 3-month intervals, as part of standard therapy in patients with relapsed or refractory follicular lymphoma.
"Most treatments for follicular lymphoma prolong the time to next treatment or progression-free survival," Vidal told The Oncology Nurse. "Rituximab, however, improves overall survival, and this is obviously a more important goal for patients."
As for which patients should not undergo rituximab maintenance therapy, she said she would probably not recommend such therapy in a patient who developed a life-threatening infection after induction chemotherapy. Also, "if a patient prefers not to receive drug treatment between chemotherapy cycles and preserve a normal lifestyle, I wouldn't argue too much," she added. "Rituximab given at disease progression may prove to have a similar effect as maintenance rituximab, although this has not yet been tested in a randomized, controlled trial."
-Jill Stein
