Targeted Therapies and Bispecific Antibodies in Second-Line Follicular Lymphoma

In the second-line management of follicular lymphoma, targeted therapies beyond chemoimmunotherapy are increasingly utilized to improve outcomes and reduce toxicity. Agents such as PI3K inhibitors, EZH2 inhibitors, and immunomodulatory combinations are employed selectively based on patient comorbidities, prior treatment history, and disease biology. Each therapy carries specific adverse events, including cytopenias, liver enzyme elevations, infections, and gastrointestinal toxicities, which require proactive monitoring and management. Epcoritamab, a bispecific antibody recently approved for this setting, has a distinct mechanism of action by simultaneously engaging T cells and malignant B cells, offering potent immune-mediated tumor control. Clinical data suggest that when combined with rituximab and lenalidomide, epcoritamab may enhance efficacy compared with R² alone. Key adverse events, such as cytokine release syndrome and immune-related effects, necessitate careful observation and prompt intervention to ensure patient safety while maximizing therapeutic benefit.