AACR 2023: Combination of Epcoritamab and Standard-of-Care Therapies for DLBCL

By: Emily Rhode
Posted: Thursday, April 20, 2023

Herve Ghesquieres, MD, PhD, of Centre Hospitalier Lyon Sud, France, and colleagues aimed to evaluate the pharmacodynamic effects of the bispecific antibody epcoritamab both as a monotherapy and in combination with standard-of-care therapies in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL). Presented during the American Association for Cancer Research Annual Meeting 2023 (Abstract 3248/21), the findings of these biomarker analyses suggest that epcoritamab monotherapy maintains its pharmacodynamic properties when combined with chemotherapeutic standard-of-care treatments both with and without rituximab.  

Patients with relapsed or refractory DLBCL from the EPCORE NHL-1 trial expansion phase as well as newly diagnosed or patients with relapsed or refractory DLBCL from the EPCORE NHL-2 trial were included in the study. The EPCORE NHL-1 cohort received 28-day cycles of subcutaneous epcoritamab, and the EPCORE NHL-2 cohort was treated with a similar dosing schedule of epcoritamab combined with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP), rituximab plus dexamethasone, cytarabine, and oxaliplatin (R-DHAX/C), and gemcitabine plus oxaliplatin (GEMOX) standard-of-care therapies. Pharmacodynamic activity was assessed using biomarkers in whole-blood samples and plasma cytokine levels.

Within the first treatment cycle, epcoritamab monotherapy and epcoritamab plus standard-of-care therapies caused a rapid and ongoing reduction in circulating peripheral B cells (CD19-positive). Circulating cytokines interferon gamma, interleukin-6 (IL-6), and IL-10 yielded a rapid, moderate response to both epcoritamab monotherapy and epcoritamab plus standard-of-care therapies approximately 24 hours after the first full dose of each. Furthermore, both epcoritamab alone and in combination with standard-of-care therapies increased levels of peripheral CD8-positive T cells expressing proliferation (Ki67) and activation (HLA-DR) markers.

Later cycles demonstrated an expansion of peripheral CD8-positive T cells and their effector memory subsets in both the monotherapy and combination therapy cohorts. Moreover, the study authors observed that most of the biomarker patterns identified in CD8-positive T cells were also expressed in peripheral CD4-positive T cells.

Disclosure: For full disclosures of the study authors, visit abstractsonline.com.

AACR Annual Meeting 2023

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