Long-term follow-up of patients with follicular lymphoma (FL) receiving single agent rituximab at two different schedules in study SAKK 35/98

Abstract

8512 Background: In FL, rituximab as a single agent obtains a response rate of 50–70% with an EFS of 1–3 years depending on the population studied. Some patients respond to this treatment for a prolonged time, so we investigated, in a clinical trial, the proportion of long-term responders and the characteristics predicting long-term response. Methods: Between 1998 and 2002, chemotherapy naïve (n = 64) or pre-treated (n = 138) FL patients received 4 weekly doses of rituximab: those responding or with stable disease were randomized to either no further treatment (observation, n = 78) or 4 additional doses of rituximab given at 2 months intervals (consolidation, n = 73). Results: At a median follow up of 8.9 years, and with all living patients having been followed for at least 5 years, the median event-free survival (EFS: time until progression, relapse, second tumor or death) is 13 months for the observation and 24 months for the consolidation arm (p=0.0012). In the observation arm 10% had no event at 5-years, the figure dropping to 4% (3/78) at 8 years, while in the consolidation arm the EFS was 26% at 5 years and remained 18% (13/73) at 8 years. The only significant prognostic factor for EFS in a multivariate Cox regression was having received consolidation rituximab (hazard ratio = 0.58, CI = 0.44–0.87, p = 0.008), whereas being chemotherapy naïve, presenting with stage < IV and showing a VV phenotype at position 158 of the Fc receptor RIIIA were not any more significantly prognostic in this long term analysis, in contrast to previous data with shorter follow-up. No long-term toxicity from treatment was observed. There were 21 cases of second malignancy: 11 on observation, 10 receiving the consolidation arm. Conclusions: It appears that the EFS advantage of prolonged versus short course rituximab continues for many years after the end of treatment. This seems to hold true independently from previous treatment, stage or 158-phenotype of the Fc receptor. Patients treated with 8 doses of rituximab over 1 year have approximately 25% and 20% chance to remain in remission at 5 and 8 years respectively. [Table: see text]