Early Rituximab Monotherapy Significantly Extends Time to Treatment in Low Tumor Burden Follicular Lymphoma

The results from 15-year follow-up data from an international phase 3 trial suggests that early rituximab monotherapy markedly prolongs time to initiation of new treatment (TTNT) for patients with advanced-stage, asymptomatic, low-tumor burden follicular lymphoma. The findings reinforce its value as a treatment strategy for patients seeking to delay chemotherapy.

The study randomized 455 patients across 3 arms: watchful waiting (n = 183), rituximab induction (n = 82), and rituximab induction followed by maintenance (n = 190). Median TTNT was 5.6 years in the watchful waiting group, 14.8 years in the rituximab induction group, and not yet reached in the rituximab maintenance group. At 15 years, 65% of patients receiving rituximab maintenance had not required new treatment, compared to 34% in the watchful waiting group.

“These mature data with 15 years of follow-up confirm that early rituximab monotherapy substantially delays the need for new treatment for patients with advanced stage, asymptomatic low tumour burden follicular lymphoma,” the researchers wrote.

Hazard ratios showed a significant reduction in risk of initiating treatment for both rituximab regimens compared to watchful waiting (HR 0.36 for rituximab maintenance; HR 0.55 for rituximab induction). No significant differences were found in overall survival, time to second new treatment, or incidence of high-grade transformation among the groups.

Notably, the benefit was more pronounced among female patients, possibly due to pharmacokinetic differences. Additionally, previously reported quality-of-life data showed improvements in emotional wellbeing and perceived disease control in patients receiving rituximab.

These findings support the use of early rituximab monotherapy as a standard treatment option in this population. It may allow a substantial proportion of patients to avoid chemotherapy altogether, particularly older adults or those with other priorities. 

Reference
Northend M, Wilson W, Ediriwickrema K, et al. Early rituximab monotherapy versus watchful waiting for advanced stage, asymptomatic, low tumour burden follicular lymphoma: long-term results of a randomised, phase 3 trial. The Lancet Haematology. 2025;12(5):e335 - e345. doi:10.1016/S2352-3026(25)00034-1.