Bispecific Antibody Therapy for Relapsed Lymphoma

Bispecific therapeutic monoclonal antibodies are an emerging treatment option for acute lymphoblastic leukemia, non-Hodgkin lymphomas, and multiple myeloma, offering immunotherapeutic efficacy via linkage of a tumor cell surface antigen and a redirected effector T cell. Investigators now report a multicenter, industry-sponsored, phase 1/2 trial of epcoritamab, which targets B-cell-expressing CD20 and T-cell CD3 antigens.

Patients with relapsed or refractory mature B-cell lymphomas received epcoritamab subcutaneously in a stepped-up dosing schedule intended to mitigate cytokine release syndrome (CRS). Treatment was given in 4-week cycles and dosed once weekly in cycles 1 to 2, biweekly in cycles 3 to 6, and once every 4 weeks from cycle 7 onward until disease progression or toxicity. Doses ranged from 12 to 60 mg; the recommended phase 2 dose was 48 mg.

Of 68 patients treated, 59% experienced CRS — all grade 1–2 and most occurring during cycle 1 — and 6% had neurologic complications. Fever and injection site reactions were common; there were no reported treatment-related deaths, although one patient died from COVID-19 while taking epcoritamab. In 46 patients with diffuse large B-cell lymphoma, the overall response rate was 68% and the complete response rate was 45% (with higher responses in the 48-mg and 60-mg cohorts); 75% of responding patients maintained response at 6 months. Four of five patients with follicular lymphoma treated at the 12-mg or 48-mg dose levels responded, with three having complete response.