The MAXIMA Study: Safety of Rituximab (MabThera®) Maintenance Therapy in Patients with Follicular Non-Hodgkin’s Lymphoma Who Have Responded to Induction Therapy.

Five randomised trials have reported that rituximab maintenance therapy leads to a progression free survival advantage in indolent NHL, with the largest trial (EORTC 20981) showing a progression-free survival benefit of 3 years in patients with follicular lymphoma compared to observation, and a significant overall survival benefit approximately halving the hazard of death. The primary objective of the current study, which involves 23 countries, initiated in August 2006, and aiming to recruit approximately 500 patients, is to extend the safety database for rituximab maintenance within a less stringent setting, allowing for a wide range of induction therapies. The study also examines the ‘real life’ safety associated with rapid-infusion of rituximab. The sample size has been calculated to detect at least one rare event with a true incidence of 0.32% with 80% power. Patients with first line or relapsed/refractory follicular lymphoma achieving a response after rituximab containing induction therapy are eligible to receive rituximab at the standard dose of 375 mg/m² every eight weeks for 2 years. One-hundred-and-thirty-nine patients have been enrolled to date for whom demographic data is available: Median age of the patient population is 56 years [range: 29 to 82]. Forty-eight percent of the patients are male. Fifty-nine percent of the patients have no relevant medical history except for NHL. Among those who do, cardiovascular diseases is the most common. Most patients (∼ 74%) have a pre-induction FLIPI score of 2 or less. Thirty-five and 49% of the patients, respectively, have grade 1 or 2 follicular NHL. Most patients (75%) have received one line of treatment (including present study induction) since diagnosis, but some patients have received up to 4 previous lines of treatment. Sixty-two percent of the patients received an anthracycline-based regimen in combination with rituximab as induction therapy, whilst 25% and 9% respectively received an alkylating-based or purine analogue-based regimen. Ninety-four patients have received at least one infusion of rituximab as maintenance therapy, less than 40% of these patients having received two or more infusions to date. In total, 162 infusions of rituximab have been administered, 25% (40/162) of these having been administered as rapid infusion. Twenty events unrelated to study medication have been reported in 9 patients, with most of these events (19/20) being CTC grade 1 or 2. There was one patient who experienced a CTC grade 1 infusion related adverse event (erythema) which was not associated with rapid infusion. At the time of the report, there were no SAEs in the clinical database, but 4 SAEs had been reported to Roche, including 1 death resulting from pre-existing cardiac arrhythmia and not related to rituximab. Based on this initial sample, there does not appear to be any safety issue associated with 2-monthly rituximab maintenance therapy, whether administered as rapid infusion or not.