Chimeric Anti-CD20 Monoclonal Antibody (Rituximab;Mabthera) in Remission Induction and Maintenance Treatment of Relapsed /Resistant Follicular Non-Hodgkin’s Lymphoma: Final Analysis of a Phase III Randomized Intergroup Clinical Trial.

Background. Last year we reported interim results of a randomised phase III trial in patients with relapsed/refractory stage III/IV positive follicular NHL, demonstrating that the addition of rituximab (R) to CHOP chemotherapy for remission induction as well as rituximab maintenance treatment significantly improves the clinical outcome (

Study design. Patients with stages III or IV follicular lymphoma at initial diagnosis and relapsed after or resistant to a maximum of two non-anthracycline containing systemic chemotherapy regimens, were randomized to remission induction with either 6 cycles of standard CHOP (once every 3 weeks) or CHOP + R (375 mg /m² at day 1 of each cycle of CHOP). Those with a complete or partial remission after 6 cycles of therapy underwent a second randomization to no further treatment (observation) or maintenance treatment with R (375 mg/m² once every 3 months) until relapse or for a maximum period of two years.

Results. At the time of the preplanned second interim analysis (February 2004) 461 patients had been included. Of these, 369 could be evaluated for response (188 CHOP; 181 R-CHOP). Both treatment arms yielded similar partial response rates (CHOP: 53.7% - R-CHOP: 52.5%), but highly significant different CR rates (CHOP: 18.1%; R-CHOP: 30.4%; p=0.0004). Of 319 patients randomized for maintenance treatment, 268 were evaluable (132 observation; 136 R maintenance). A highly significant advantage was observed in progression free survival in patients randomized to R maintenance, when compared with the observation arm (median PFS 38 vs.15 months; p<0.0001). At that time there was no impact on OS: the observed difference (in favor of R maintenance) was not significant for an interim analysis. Toxicity of CHOP and R-CHOP induction was similar, and R maintenance was associated with minimal toxicity. These results of the planned second interim analysis showed that the formal criteria for stopping the trial had been met. It was concluded that this is the first trial to show that: 1) in patients with relapsed/resistant follicular lymphoma R-CHOP remission induction results in a highly significant increase in CR rate as compared to CHOP; 2) rituximab maintenance treatment significantly improves PFS in patients responding to induction treatment. The final analysis of the study results will be performed in September 2005, with an additional follow-up of at least 18 months. The final results will be presented at the meeting.