Maintenance Rituximab Every 2 Months for 2 Years Is Effective and Well Tolerated In Patients with Follicular Lymphoma with Both Standard or Rapid Infusion: Updated Results From the Phase IIIb MAXIMA Study

MAXIMA is a Phase IIIb study evaluating the safety of rituximab (Rituxan®, MabThera®) maintenance therapy given at either a standard infusion rate or as a rapid infusion in patients with treatment-naïve or previously treated follicular lymphoma (FL) responding to induction treatment. The study also aims at confirming the effectiveness of rituximab maintenance therapy with respect to improvement of progression-free survival and overall survival, and the rate of conversion from partial response (PR) to complete response/unconfirmed complete response (CR/CRu) whilst on maintenance. Data are described here at a median follow-up of 28.8 months.

Patients from 211 centers in 24 countries who achieved a CR/CRu or PR following induction therapy with 8 cycles of a rituximab-containing regimen, received maintenance treatment with rituximab (375 mg/m²) every 2 months for a maximum of 2 years. Rituximab could be administered at a standard infusion rate (>90 minutes) or as a rapid infusion (≤90 minutes), depending on the standard practice at each center.

A total of 545 patients responding to induction treatment were enrolled. Median age of the patients was 57 years (range 29–86), with 11.7% over 70 years. 395 (72.5%) patients were previously untreated. 381 (69.9%) patients entered the study in CR/CRu after induction and 164 (30.1%) in PR. Of the 381 patients with post-induction CR/CRu, 353 (92.7%) remained in CR/CRu during maintenance (progressive disease 7.1%; missing 0.3%). Of the 164 patients achieving PR during induction, 11 patients (6.7%) converted to CR/CRu during maintenance. The full course of maintenance therapy was completed by 407 patients (74.7%). For the 137 patients who did not complete rituximab maintenance, reasons for premature discontinuation were disease progression (58 patients), treatment toxicity which was low (16 patients), voluntary pt withdrawal (11 pts), death (5 pts) and other reasons (47 pts) accounted for the remainder. Rituximab maintenance every 2 months for 2 years was very well tolerated. In the safety population of 534 patients, a total of 52 infusion-related adverse events (AEs) occurred in 31 patients (5.8%), with hypotension (5 patients), pyrexia (3 patients), hypertension (3 patients), headaches (3 patients), insomnia (2 patients) and erythema (3 patients) being the most commonly reported side effects. No differences in infusion-related AEs were observed by infusion schedule, with AEs occurring with 0.9% of standard infusions and 0.5% of rapid infusions (Table).The majority of infusion-related AEs were Grade 1 (42/52). One infusion-related serious adverse event (SAE), a Grade 4 cerebrovascular accident, was reported. Other AEs were observed in 336 patients (62.9%), with the majority of these being Grade 1–2. Grade 3, 4 and 5 AEs occurred in 86 (16.1%), 30 (5.6%) and 9 patients (1.7%), respectively. Rituximab-related AEs were rare being reported in 57 patients (10.7%) and accounting for only 6.1% (105/1721) of all AEs. The most common rituximab-related AEs were infections, occurring in 22 patients (4.1%). Two Grade 5 rituximab-related AEs were reported; 1 liver disorder and 1 cerebral hemorrhage. A total of 141 SAEs occurred in 104 patients; of these, only 19 events in 15 patients were deemed to be related to rituximab. The most common rituximab-related AE was pneumonia with 3 events reported.

Maintenance rituximab was well tolerated with little rituximab-related toxicity. Treatment was associated with few infusion-related AEs, and there was no apparent difference in tolerability when rituximab was administered as a standard or rapid infusion. This study provides additional support for the use of rituximab maintenance every 2 months for 2 years following rituximab-containing induction therapy for patients with newly diagnosed or previously treated FL.

Foá:Roche: Membership on an entity's Board of Directors or advisory committees. Off Label Use: Rituximab is broadly approved for the treatment of FL however the specific use and therapeutic lines may represent some off-label use. van Hazel:Roche: Membership on an entity's Board of Directors or advisory committees.