Overall Survival and Side Effects
The European Organization for Research and Treatment of Cancer also conducted an assessment of rituximab first-line maintenance therapy. The EORTC 20981 trial enrolled 334 patients who had experienced complete or partial remission in response to induction therapy with either six cycles of CHOP or rituximab plus CHOP. They were randomly assigned to receive either rituximab maintenance treatment every three months or to be observed only. The study had a median follow-up of six years. Rituximab maintenance was seen to significantly improve PFS, with a median of 3.7 years compared to 1.3 years for the observation group.
OS at five years was 74% among patients receiving rituximab maintenance and 64% in the observation arm, which was not a statistically significant improvement. Patients who relapsed prior to the five-year endpoint were treated with rituximab as “salvage therapy.” Fifty-nine percent of the original CHOP followed by observation patients and 26% of R-CHOP followed by rituximab maintenance patients had a 9.7% and 2.4% increase in grades 3 and 4 infections, respectively.
Another study, published in the Journal of the National Cancer Institute, and headed by Liat Vidal, M.D., of the Rabin Medical Center in Israel, pooled data from five randomized trials involving 1,143 adult patients that compared maintenance therapy with no maintenance therapy. Most patients had FL that had relapsed or become refractory. The trials were conducted between 1998 and 2004.
OS data was available for 985 patients. Rituximab maintenance therapy was associated with a 40% improvement in OS relative to observation or retreatment with rituximab at relapse. The improvement in OS was statistically significant for patients with relapsed or refractory lymphoma but not for previously untreated patients.
Study investigators concluded, “Our results suggest that rituximab maintenance therapy for up to two years, either as four weekly infusions every six months or as a single infusion every two to three months, should be added to standard therapy of patients with relapsed or refractory follicular lymphoma after successful induction treatment.”
They added, however, that “the higher rate of infections with rituximab therapy should be taken into consideration when making treatment decisions.” Patients treated with rituximab maintenance therapy had nearly twice the rate of infection-related adverse events as patients who did not have prolonged rituximab therapy.
Wyndham Wilson, M.D., Ph.D., chief, lymphoid therapeutics section, Center for Cancer Research at the NCI, noted, “We know that patients with follicular lymphoma benefit from treatment with rituximab, but we cannot conclude from this analysis that maintenance therapy is the optimal approach to administering rituximab.”