Rituximab Monotherapy for Previously Untreated Follicular Lymphoma: Which Approach Is Better?

Patients with asymptomatic, low-tumor-burden follicular lymphoma (FL) can be managed by a watch-and-wait strategy or, as shown in several clinical trials, by single-agent intravenous (IV) rituximab; this second approach has the intent of delaying time to disease progression and cytotoxic chemotherapy. Investigators now report a phase 3, multicenter, randomized trial comparing industry-supplied rituximab IV with subcutaneously administered rituximab in 202 patients with previously untreated FL (stage II–IV; grade 1, 2, or 3a) and with low tumor burden by GELF (Groupe d'Etude des Lymphomes Folliculaires) criteria.

The two treatment arms were IV rituximab 375 mg/m² weekly for 4 weeks or a subcutaneous regimen, which started with one IV rituximab dose, then fixed-dose subcutaneous (1400 mg) weekly for 3 more weeks, and finally maintenance bimonthly subcutaneous rituximab through month 9. The progression-free survival (primary endpoint) at 4 years was significantly better with subcutaneous than with IV rituximab (58.1% vs. 41.2%; hazard ratio, 0.585). Using Lugano criteria (which includes restaging positron-emission tomography/computed tomography and bone marrow biopsy), the overall response rate was significantly better with subcutaneous than IV rituximab (73% vs. 52%), as was the complete response rate (59% vs. 36%). The groups did not differ on 4-year overall survival (95%–97%) or time to next lymphoma treatment. Toxicities were as expected and did not differ between study arms. In exploratory analyses, higher rituximab area-under-the-curve (AUC) serum levels during the first 3 months of therapy correlated with better outcomes and with subcutaneous rituximab.