Early rituximab vs watchful waiting in low-tumor-burden FL: Long-term results of a phase III trial

Initial results of a phase III, randomized trial (NCT00112931) in patients with follicular lymphoma (FL) treated with rituximab monotherapy vs watchful waiting demonstrated improved time to new treatment (TTNT) after a median follow-up of 4 years. Given the natural lengthy course of FL, the trial was further extended. Northend et al. published long-term results with a 15-year follow-up in The Lancet Hematology.

From October 15, 2004, to May 1, 2009, adult patients with asymptomatic, Stage 2–4, Grade 1–3a low-tumor-burden FL and Eastern Cooperative Oncology Group performance status 0–1 (N = 455) were randomly assigned to the rituximab induction (n = 82), rituximab maintenance (n = 190), or watchful waiting (n = 183) group. The primary endpoint was TTNT. The median follow-up was 14.7 years.

Key learnings

The median TTNT was NR, 14.8 years, and 5.6 years, while the proportion of patients not requiring new treatment at 15 years was 65%, 48%, and 34%, in the rituximab maintenance, induction, and watchful waiting groups, respectively. 

The rituximab induction and maintenance groups were less likely to initiate new treatment compared with the watchful waiting group (HR, 0.55; 95% CI, 0.38–0.80; p = 0.0019 and HR, 0.36; 95% CI, 0.26–0.50; p < 0.0001, respectively).

There were no differences in TT2NT, OS, cause-specific mortality, and high-grade transformation rates between the rituximab maintenance, induction, and watchful waiting groups.

Early rituximab monotherapy substantially delays the need for new treatment, offering a treatment option for patients with advanced-stage, asymptomatic low-tumor-burden FL, particularly in those who wish to delay or avoid chemotherapy.