Follicular Lymphoma: Treatment

Follicular Lymphoma: overview

This algorithm addresses treatment of grade 1 to 3a follicular lymphoma, with tumor burden as the first branch point. For low-burden or asymptomatic disease, observation (watchful waiting) is the default, with rituximab monotherapy if treatment is desired (RESORT). For high-burden disease meeting GELF criteria, the options are bendamustine plus rituximab followed by rituximab maintenance (StiL) or obinutuzumab plus chemotherapy (GALLIUM). The site's GALLIUM summary notes improved PFS over rituximab-based chemotherapy but greater toxicity and no OS benefit.

For relapsed or refractory disease, the chart lists lenalidomide plus rituximab (AUGMENT), CD19 CAR-T therapy (ZUMA-5), the bispecific antibody mosunetuzumab, and tazemetostat for EZH2-mutant disease. In AUGMENT, lenalidomide plus rituximab improved median PFS (39.4 vs 14.1 months, HR 0.46) with an OS benefit emerging at 5 years, making it a preferred chemotherapy-free option for patients who are not rituximab-refractory. ZUMA-5 showed a 94% response rate and 79% complete response rate with axicabtagene ciloleucel in heavily pretreated disease, with durable remissions.

Trials behind this algorithm

• RESORT (E4402) Kahl BS et al, JCO, 2024; PMID: 38194625
• StiL trial Rummel MJ et al, 2013, Lancet, PMI:D 23433739
• GALLIUM Marcus R et al, NEJM, 2017; PMID: 28976863
• AUGMENT Leonard JP et al, JCO, 2019; PMID: 30897038
• ZUMA-5 Jacobson CA et al, Lancet Oncol, 2022; PMID: 34895487
• Mosunetuzumab (FL) Budde LE et al, Lancet Oncol, 2022; PMID: 35803286
• Tazemetostat FL Morschhauser F et al, Lancet Oncol, 2020; PMID: 33035457

Background reading: Follicular lymphoma (FL) board review notes.