Follicular Lymphoma: Novel Therapies and Strategies for Optimal Therapeutic Sequencing

Follicular lymphoma (FL) is the most common indolent non-Hodgkin lymphoma, characterized by a relapsing and remitting course and a median overall survival exceeding 15-20 years with modern therapy. While chemoimmunotherapy remains the cornerstone of frontline management, the rapid approval of novel agents, including bispecific antibodies, CAR T-cell products, and antibody-drug conjugates, has fundamentally reshaped the relapsed/refractory (R/R) landscape. This review summarizes current evidence across the treatment continuum and propose a practical, risk-adapted sequencing framework.

Bispecific antibodies (mosunetuzumab, epcoritamab) have demonstrated durable complete responses in heavily pretreated FL, with manageable toxicity profiles. CAR T-cell therapy (axicabtagene ciloleucel, lisocabtagene maraleucel, and tisagenlecleucel) are approved in R/R FL after two or more prior lines, offering high response rates albeit notable logistal and safety considerations. Frontline trials incorporating lenalidomide-rituximab have established chemotherapy-free option with long-term outcomes comparable to chemoimmunotherapy. Emerging data on antibody-drug conjugates and bispecific antibody combination therapy continue to expand the therapeutic arsenal. Despite favorable long-term outcomes for many patients with FL, relapse remains common and remission typically shortens with successive lines of therapy. The growing number of effective agents with distinct mechanisms of action creates both opportunity and complexity. Evidence-based sequencing strategies that account for prior therapy exposure, patient fitness and mechanism-specific considerations are increasingly critical to maximizing outcomes across the disease trajectory.