Bispecific antibodies, specifically anti-CD20 T-cell engaging constructs, are poised to alter the treatment paradigm of multiple B-cell malignancies, including follicular lymphoma. Two CD20xCD3 bispecific antibodies, mosunetuzumab and epcoritamab, are now approved in the United States for third-line or later treatment of follicular lymphoma. A third agent, odronextamab, remains under review by regulatory agencies. In pivotal phase II trials, these bispecific antibodies demonstrated overall response rates of approximately 80%, with complete response rates of 60-70%, the majority of which have been durable at two years. Important safety signals included risk of infections, neutropenia, and cytokine release syndrome, which occurred in approximately half of patients, but was rarely high grade. Despite similar efficacy and toxicity profiles, key differences exist among agents, primarily relating to treatment duration, route of administration, and prophylactic corticosteroid use. Several ongoing studies are exploring bispecific antibodies in earlier lines of treatment, either as single agents or in combination with other active therapies. This novel class of agents is likely to play a pivotal role in improving outcomes for patients with follicular lymphoma.
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