Responses were seen in 68% of patients with DLBCL and 90% of patients with follicular lymphoma.

  • Major Finding: Responses were seen in 68% of patients with DLBCL and 90% of patients with follicular lymphoma.

  • Concept: In this phase I/II trial, there was no dose-limiting toxicity or grade ≥ 3 cytokine release syndrome.

  • Impact: This work supports ongoing phase II investigation of epcoritamab treatment in non-Hodgkin lymphoma.

The treatment of relapsed or refractory non-Hodgkin lymphomas has been revolutionized by novel immunotherapy approaches, such as chimeric antigen receptor T-cell therapies, but problems with patient access and toxicity remain. In a phase I/II, first-in-human clinical trial, Hutchings and colleagues evaluated the CD3- and CD20-targeting bispecific antibody epcoritamab—which had been shown preclinically to cause T-cell activation and expansion and to induce T cell–mediated control of CD20+ tumor cells—in 73 patients with relapsed or refractory CD20+ non-Hodgkin lymphoma, mostly diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma. Among patients with DLBCL, the overall response rate was 68%, and 45% exhibited complete responses, with all patients who had complete responses still being in remission at the data cutoff after a median follow-up period of 9.2 months. Among patients with follicular lymphoma, 90% of patients exhibited responses, and 50% of patients experienced complete responses; at the data cutoff, progression-free survival data for patients with follicular lymphoma whose disease responded to treatment were immature. Additionally, in patients who had detectable B cells before treatment, epcoritamab therapy resulted in rapid and sustained reductions in the number of circulating peripheral B cells along with increases in the number of circulating T cells. Notably, no dose-limiting toxicities occurred, and all incidences of cytokine release syndrome (CRS) were limited to grade 1 or 2. Common adverse events included pyrexia, which was typically associated with CRS and occurred in 69% of patients, and injection-site reactions, which occurred in 47% of patients. In summary, the results of this trial show that epcoritamab is safe and produces antitumor responses in patients with non-Hodgkin lymphoma, supporting the ongoing phase II study of this treatment.

Hutchings M, Mous R, Clausen MR, Johnson P, Linton KM, Chamuleau MED, et al. Dose escalation of subcutaneous epcoritamab in patients with relapsed or refractory B-cell non-Hodgkin lymphoma: an open-label, phase 1/2 study. Lancet 2021;398:1157–69.

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