Current immunotherapeutic approaches for relapsed/refractory follicular lymphoma: bispecific antibodies and CAR T-Cell therapies

Chemoimmunotherapy (CIT) combines anti-CD20 monoclonal antibodies with chemotherapy and has long been the standard first-line treatment for follicular lymphoma (FL). However, a significant subset of patients, particularly those who experience disease progression within 24 months (POD24), continue to experience poor long-term outcomes. Conventional salvage therapies offer limited benefits for high-risk individuals, highlighting the urgent need for novel treatment strategies. T-cell redirecting therapies, including chimeric antigen receptor (CAR) T-cell products and bispecific antibodies (BsAbs), have emerged as effective options in the relapsed/refractory (R/R) setting, demonstrating high response rates and durable remissions, even among patients with POD24 or refractory disease. Although CAR T-cell therapies are associated with deeper and more sustained responses, they also have higher toxicity and greater logistical complexity. In contrast, BsAbs such as mosunetuzumab and epcoritamab offer favorable safety profiles, off-the-shelf availability, and the potential for outpatient administration. Ongoing clinical trials are actively investigating the integration of BsAbs into earlier lines of therapy, including frontline settings, with encouraging results. However, in Korea, access to CAR T-cell therapies and BsAbs remains limited to clinical trials, highlighting the need for broader clinical availability. Ultimately, treatment selection and sequencing should be personalized based on patient comorbidities, prior therapies, tumor biology, and urgency of disease control. As the treatment landscape continues to evolve, immunotherapeutic modalities are expected to play a central role in improving the outcomes of patients with FL.