Rituximab Maintenance for Two Years in Previously Untreated Follicular Lymphoma: No Difference in Outcome between Patients Receiving Treatment at Two Month Versus Three Month Interval

Rituximab maintenance (MR) improves progression free survival (PFS) in patients with follicular lymphoma after induction treatment. The PRIMA trial demonstrated a PFS benefit using a maintenance protocol in which rituximab was administered every 2 months in previously untreated follicular lymphoma (Salles et al, Lancet 2011). The EORTC 20981 trial showed a similar benefit in relapsed or refractory follicular lymphoma using a schedule in which rituximab was administered every 3 months (Van Oers et al. JCO 2010). These maintenance protocols have not been formally compared. This multi-center retrospective study compares the clinical outcome of patients with previously untreated follicular lymphoma receiving MR at 3 month intervals versus 2 month intervals.

A total of 112 patients completed MR for follicular lymphoma after first line induction between 2005 and 2015: 71 (63%) received MR at 3 month interval and 41 (37%) at a 2 month interval. The GELF criteria (Brice et als, JCO, 1997) were met in 41 (59%) patients in the 3 month interval group and in 33 (79%) patients in the 2 month interval group. All patients received an induction regimen containing rituximab and 78% received R-CVP. Median follow up time was 59 months and was significantly longer in the 3 month interval group with 70 months compared to 40 months in the 2 month interval group (p < 0.001). Before the publication of PRIMA, most patients with previously untreated follicular lymphoma received MR at a 3 month interval which explains the longer follow up in this group. Progression was documented in 14 (20%) of the patients in the 3 month interval group and in 11 (26%) in the 2 month interval group. PFS at 40 months was similar in both groups with 88% in the 3 month interval group and 80% in the 2 month interval group (HR 0.454, 95% CI: 0.202 - 1.021, p 0.056). Twelve (17%) of the patients in the 3 month interval group and 8 (19%) in the 2 month interval group required second line therapy. Time to next treatment was not reached in either group. Treatment free survival at 40 months was similar between the two groups with 91% in the 3 month interval group compared to 80% in the 2 month interval group (HR 0.487, 95% CI: 0.193 - 1.230, p 0.128). Six (9%) of the patients in the 3 month interval group died, 4 (6%) of these deaths were attributed to the lymphoma, and 1 (2%) patient died in the 2 month interval group. Overall survival at 40 months was not statistically different between the 3 and 2 month interval groups with 96% and 100% respectively (HR 1.761, 95% CI: 0.194 - 15.982, p 0.615).

The administration of MR at an interval of 3 months compared to 2 months does not seem to adversely affect the survival outcomes of patients with previously untreated follicular lymphoma. The administration of rituximab every 3 months instead of every 2 months would decrease the cost and potentially the infectious complications of MR. Although this study has limitations, such as a limited number of patients and a disparity between the two groups regarding the presence of GELF criteria, it provides preliminary data supporting the interest of further investigation of the administration of MR every 3 months in previously untreated follicular lymphoma.