Clinical Advances in Hematology & OncologyEpcoritamab, a Promising Therapy for Richter Syndrome?

Epcoritamab: A Novel Approach in the Battle Against Richter Syndrome

In the relentless pursuit of advancing treatment for Richter syndrome (RS), a formidable challenge in the realm of hematologic malignancies, epcoritamab emerges as a beacon of hope. This Q&A with Arnon Kater, MD, PhD, a Professor of Hematology and Deputy Head of Department at the Lymphoma and Myeloma Research in Amsterdam, the Netherlands, explores the intricacies of epcoritamab’s mechanism, its clinical evaluation in RS, and its potential to reshape the therapeutic landscape, offering a new avenue for patients grappling with this aggressive lymphoma transformation.

Key Points:

• Richter syndrome (RS) is the transformation of chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) into an aggressive lymphoma, predominantly diffuse large B-cell lymphoma (DLBCL).
• Epcoritamab, a bispecific antibody targeting CD3 on T cells and CD20 on B cells, activates T-cell–mediated killing of malignant B cells, offering a new treatment modality for RS.
• The EPCORE CLL-1 study, focusing on epcoritamab in CLL and RS, demonstrated a 60% overall response rate in RS patients, showcasing significant efficacy in a difficult-to-treat population.
• Epcoritamab’s administration protocol includes step-up dosing and corticosteroid prophylaxis to mitigate cytokine release syndrome (CRS), a common side effect associated with T-cell activation therapies.
• The study’s findings suggest epcoritamab could serve as a promising monotherapy or in combination with other agents like BTK inhibitors or checkpoint inhibitors for RS treatment.
• Comparatively, epcoritamab presents a potential advancement over current RS treatments, which generally yield temporary effects with chemoimmunotherapy or limited success rates in monotherapies.
• Ongoing research aims to explore epcoritamab in various combinations, potentially setting a new standard in RS therapeutic strategies.

“This study [EPCORE CLL-1] demonstrates for the first time that bispecific antibodies are a mechanism to activate autologous T cells and are beneficial and effective in this disease.”
– Arnon Kater, MD, PhD

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