Phase 2 studies suggest that the monoclonal antibody rituximab may improve the prognosis of patients with follicular lymphoma (FL) when it is added to chemotherapy. In the current study, 428 patients with untreated, advanced-stage FL were randomly assigned for therapy with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) alone (n ‫؍‬ 205) or CHOP combined with rituximab (R-CHOP) (n ‫؍‬ 223). R-CHOP reduced the relative risk for treatment failure by 60% and significantly prolonged the time to treatment failure (P < .001). In addition, a significantly higher overall response rate (96% vs 90%; P ‫؍‬ .011) and a prolonged duration of remission (P ‫؍‬ .001) were achieved. In spite of a relatively short observation time, these beneficial effects even translated to superior overall survival (P ‫؍‬ .016), with 6 deaths in the R-CHOP group compared with 17 deaths in the CHOP group within the first 3 years. The predominant treatment-related adverse effect was myelosuppression. Severe granulocytopenia was more frequently observed after R-CHOP (63% vs 53%; P ‫؍‬ .01). However, severe infections were rare and of similar frequency after R-CHOP and CHOP (5% and 7%

FLO reduced toxicity as compared with FLP. In older adult patients, FLO also seemed to be associated with improved efficacy.