Treatment of Follicular Lymphoma With CHOP and Anti-CD20 Therapy: 15-Year Follow-Up of the SWOG S0016 Trial.

Importance: Follicular lymphoma (FL) has historically been regarded as incurable, with patients experiencing late relapses after initial chemoimmunotherapy treatment. Objective: To provide 15-year follow-up data from the SWOG S0016 trial that evaluated the potential for long-term remission and cure following chemoimmunotherapy with cyclophosphamide, hydroxydaunorubicin/doxorubicin, oncovin, and prednisone/prednisolone (CHOP)-based regimens. Design, Setting, and Participants: This multicenter, intergroup study was conducted at academic and community practice locations throughout the US and enrolled patients with untreated, advanced-stage FL. Cure modeling, which involves estimating the proportion of patients cured of the disease, was conducted by incorporating background mortality rates to estimate the proportion of patients cured of FL during the S0016 trial. Patients were enrolled between May 2001 and October 2008 and followed up for a median (IQR) of 15.5 (13.6-16.9) years. The 15-year analysis was conducted in June 2025. Interventions: Patients were randomized to receive either rituximab plus CHOP (R-CHOP) or CHOP followed by radioimmunotherapy (CHOP-RIT). Main Outcomes: The main outcomes were 15-year progression free survival (PFS) and overall survival (OS). Secondary outcomes included cure modeling. Results: A total of 531 eligible patients (242 female patients [46%]; median [IQR] age, 53 [45-61] years) were included in the final analysis (267 [50%] received R-CHOP and 264 [50%] CHOP-RIT). The overall 15-year OS was 70%, with no significant difference between treatment arms, and the 15-year PFS was 40% (95% CI, 36.0%-44.7%). CHOP-RIT demonstrated superior 15-year PFS (47% vs 34%; P = .004) compared with R-CHOP. Cure modeling estimated an overall cure rate of 42%, with the highest cure rates observed in patients with low Follicular Lymphoma International Prognostic Index scores and normal β2 microglobulin levels. The rate of relapse declined substantially over time, from 6.8% during the first 5 years to 0.6% between 15 to 20 years. Conclusions and Relevance: The results of this secondary analysis suggest that a subset of patients with advanced-stage FL can achieve cure with CHOP-based chemoimmunotherapy, as relapse rates decline over time. This finding represents a paradigm shift in the understanding of and approach to FL, with implications for initial patient discussions and future research strategies. Trial Registration: ClinicalTrials.gov Identifier: NCT00006721.