Julio Delgado, MD, CRI Clinical Innovator Institut d'Investigacions Biomèdiques August Pi i Sunyer (Spain) Area of Research: Lymphoma Richter’s Transformation Syndrome (RT) is a grave complication of chronic lymphocytic leukemia (CLL), leading to aggressive lymphoma and poor patient outcomes. Current treatments, including R-CHOP therapy and hematopoietic cell transplantation, offer limited success, resulting in frequent relapses. Innovative strategies are urgently needed to improve survival prospects. Chimeric antigen receptor T-cells (CAR-T), particularly CART19 targeting CD19, have shown promise in B-cell malignancies but are not effective for RT patients. In previous clinical studies, Dr. Delgado’s ARI-0001 CAR-T product achieved an 82% response rate but exhibited CD19-negative relapses. To address this, a novel dual CAR-T cell, ARI-0003, targeting CD19 and CD269 (BCMA), was developed. This approach capitalizes on co-expression of CD19 and CD269 in lymphoma and overcomes CD19 antigenic loss. Preclinical data demonstrated the superiority of ARI-0003 in eradicating RT cells. Therefore, a single-arm pilot trial is proposed to assess the safety and efficacy of ARI-0003 in adult patients with refractory RT. The study aims to provide a durable response and potentially a curative option for patients with high unmet medical needs, addressing the formidable challenge of Richter’s transformation and improving patient outcomes in this challenging disease. Projects and Grants RICHARDIII: A pilot study on the use of ARI-0003 cells (dual anti-CD19/CD269 chimeric antigen receptor T-cells) for patients with relapsed/refractory Richter’s transformation Institut d’Investigacions Biomèdiques August Pi i Sunyer (Spain) | Lymphoma | 2024
