Between April 1995 and March 1996, 166 patients from 31 centres with relapsed or refractory CD20+ low grade or follicular B-cell lymphoma were enrolled in a phase III intent to treat study to examine the efficacy of rituximab given once weekly for 4 consecutive weeks.r
A subsequent single centre, single arm, phase II study established the safety and efficacy of an 8 week course of rituximab in the same patient population (Piro et al, 1999).
Ghielmini et al (2004) conducted a randomised comparison of the standard 4 week regimen with a prolonged regimen (standard regimen followed by an extra dose every 2 months x 4). 202 patients from 25 institutions with newly diagnosed or refractory/relapsed follicular lymphoma were enrolled between January 1998 and February 2001.r
In 2010 van Oers et al published the long term outcomes (median follow up of 6 years) of the EORTC phase III trial on the role of rituximab maintenance treatment in relapsed/resistant follicular non Hodgkin lymphoma. After first receiving induction of CHOP (n = 231) or R-CHOP (n = 234), patients were then randomly assigned to receive either rituximab maintenance (rituximab 375 mg/m2 IV every 3 months until relapse or maximum of 2 years) (n =167) or observation (n = 167).r
In McLaughlin et al (1998), 6% patients achieved complete remission and 42% partial response. Of the remaining patients, 56 of 75 demonstrated at least a decrease in measurable disease. At a median follow-up of 11.8 months, projected time to progression was 13 months with 53 of the 76 patients who responded having not relapsed.r
Of 185 evaluable patients in Ghielmini et al (2004), ORR was 52% with 8% CR following the standard 4 weekly schedule of rituximab. Chemotherapy naive patients demonstrated a statistically significantly (p=0.0097) greater RR of 67% with 9% CR when compared to those who had been previously treated - RR 46%, CR 8%. EFS in those randomised to receive the standard rituximab schedule was 11.8 months.r
In van Oers et al, the advantage of rituximab maintenance was observed after both CHOP and R-CHOP. After CHOP, the maintenance rituximab arm had a PFS of 3.1 years vs 1 year in the observation arm (P < 0.001); and after R-CHOP, maintenance rituximab arm had a PFS of 4.4 years vs 1.9 year in the observation arm (P< 0.043).r
The most common adverse reactions of rituximab (incidence = 25%) observed in patients with relapsed or refractory low-grade or follicular NHL are infusion reactions, fever, chills, infection, asthenia, and lymphopenia. Respiratory system events were reported in 38% of patients, and 31% reported infectious events. Grade 3 and 4 cytopenias were reported in 48% of patients and included lymphopenia (40%), neutropenia (6%), leukopenia (4%), anemia (3%), and thrombocytopenia (2%).
Maintenance rituximab treatment was well tolerated, with the only significant toxicity being an increase in grade 3 to 4 neutropenia (11.5% of patients vs 6% in the observation arm), contributing to the overall increased infection rate of 9.7% in the maintenance rituximab arm (vs 2.4% in the observation arm). r