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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.
Comment
Epcoritamab produced high response rates in this early-phase clinical trial, thus joining a cadre of other bispecifics in development for relapsed/refractory B-cell lymphomas. Of note, all four patients who had failed prior chimeric antigen receptor T-cell (CAR-T) therapy responded, while epcoritamab served as a bridge to consolidative stem cell transplantation in several others. Advantages of a bispecific include being “off-the-shelf” and thus more quickly deployed than CAR-T in rapidly progressing disease settings. Longer follow-up of both CAR-T and bispecifics is needed to identify preferred approaches among subgroups of aggressive and follicular lymphomas.
Citation(s)
Author:
Hutchings M et al.
Title:
Dose escalation of subcutaneous epcoritamab in patients with relapsed or refractory B-cell non-Hodgkin lymphoma: An open-label, phase 1/2 study.
Source:
Lancet
2021
Sep
25; [e-pub].
(Abstract/FREE Full Text)
Author:
Ghobadi A and Bartlett NL.
Title:
CD3xCD20 bispecific T-cell redirectors for relapsed or refractory B-cell lymphoma.
Source:
Lancet
2021
Sep
25; [e-pub].
(Abstract/FREE Full Text)
Empfohlen von
Michael E. Williams, MD, ScM