Dr Smith on Bispecific Antibodies for the Management of R/R Follicular Lymphoma

Sonali M. Smith, MD, Elwood V. Jensen Professorship of Medicine, chief, Section of Hematology/Oncology, The University of Chicago Medicine, discusses the currently available arsenal of bispecific antibodies used for the management of relapsed/refractory follicular lymphoma.

Bispecific antibodies are extremely active in the relapsed and refractory setting for follicular lymphoma, Smith begins. Currently, there are 2 bispecific antibodies approved by the FDA for use in patients with relapsed/refractory follicular lymphoma following 2 or more lines of systemic therapy. The FDA-approved agent,mosunetuzumab-axgb (Lunsumio), gained approval in December 2022, and epcoritamab-bysp (Epkinly), was approved in July 2024. Both agents target CD20 and CD3, but they have distinct structural and clinical features, Smith explains.

Mosunetuzumab has an engineered Fc portion designed to reduce toxicity, and it targets the same epitope on CD20 as rituximab (Rituxan), she states. This bispecific antibody is administered with a ramp-up dosing phase in the first cycle, followed by administration every 21 days for up to 17 cycles. Notably, the treatment includes a response-directed pause after the eighth cycle, allowing for potential adjustments based on patient response, Smith says.

Epcoritamab also features an engineered Fc portion with specific mutations aimed at minimizing toxicity, she continues. This agent is unique in that it is primarily administered subcutaneously, which is advantageous for patient convenience and safety, Smith details. Epcoritamab also employs a step-up dosing phase during the first 2 cycles to mitigate adverse effects such as cytokine release syndrome, she notes. The administration of dexamethasone during the ramp-up phase further helps manage these early toxicities, Smith reiterates.

In addition to mosunetuzumab and epcoritamab, odronextamab (REGN1979), another bispecific antibody approved outside the United States, has demonstrated high efficacy, Smith adds. The agent was granted FDA priority review for relapsed/refractory follicular lymphoma and diffuse large B-cell lymphoma in September 2023. However, in March 2024, the FDA issued complete response letters to the biologics license applications seeking the agent's approval for these indications related to enrollment status in confirmatory trials.

All 3 agents exhibit overall response rates of approximately 80%, with complete response rates at approximately 60%. These outcomes are particularly notable given the challenging nature of treating patients with relapsed/refractory FL, Smith concludes.