Journal Article

CD19 CAR T‐Cell Therapy in Richter Transformation: A Multicentre Retrospective Analysis by the European Research Initiative on Chronic Lymphocytic Leukaemia

Danylesko, Ivetta, Stamatopoulos, Kostas, Yerushalmi, Ronit, Amit, Odelia, Visentin, Andrea, Gabrielli, Giulia, Marcus, Ronit, Herishanu, Yair, Martinez‐Cibrian, Nuria, Benjamini, Ohad, Scarfo, Lydia, Nagler, Arnon, Chatzikonstantinou, Thomas, Avigdor, Abraham, Leiba, Ronit, Gentile, Massimo, Avni, Batia, Grisariu, Sigal, Fineman, Riva, Beyar‐Katz, Ofrat, Ram, Ron, Shouval, Roni, Ruella, Marco, Paruzzo, Luca, Shem‐Tov, Noga, Tadmor, Tamar, Ortiz‐Maldonado, Valentin, Schuster, Stephen J., Vandenberghe, Elisabeth, Shimoni, Avichai, Delgado, Julio, Ghilardi, Guido, Zuckerman, Tsila, Minga, Eva, Ghia, Paolo

2025

Overview

Richter transformation (RT) is a serious complication of chronic lymphocytic leukaemia (CLL), with poor outcomes. While CAR T‐cells have shown promise in large B‐cell lymphoma, their efficacy in RT remains unclear, and the role of allogeneic stem cell transplant (alloSCT) post‐CAR T‐cells has not been established. This study aimed to assess the clinical response and survival of patients with RT treated with anti‐CD19 CAR T‐cells. This retrospective multicentre study, conducted by the European Research Initiative on CLL (ERIC), included patients with RT who received anti‐CD19 CAR T‐cells between 06/2018 and 01/2024. Progression‐free survival (PFS) and overall survival (OS) were evaluated from CAR T‐cell infusion. Fifty‐four patients with RT were treated with anti‐CD19 CAR T‐cells (academic products, n = 29; commercial products, n = 25). The median age was 63 years, with 72% having an ECOG performance status (PS) of 0 to 1. Seven patients (13%) underwent alloSCT following CAR T‐cell infusion, with the indications being consolidation therapy (n = 4) and relapse/progression (n = 3). The overall response rate was 65%, with 46% achieving complete response (CR) at 1 month and 50% at 3 months. The median PFS was 8.0 months (95% CI: 2.1–13.8) and the median OS was 14.4 months (95% CI: 8.8–19.2). The median PFS was 31.6 months for patients achieving CR at 1 or 3 months post CAR T‐cells. Significant factors associated with mortality included high ECOG PS (p < 0.001), high LDH at CAR T infusion (p = 0.005), ICANS (p = 0.046) and no response at 1 month (p = 0.02). Multivariable Cox regression analysis identified treatment response at 1 month (p = 0.001) and increasing age (p = 0.5) as significant predictors of mortality. This study shows encouraging response rates and manageable toxicity for patients with RT treated with both academic and commercially available CAR T‐cell products.

• Publisher: John Wiley & Sons, Inc
• Subject: Adult / Aged / allogeneic SCT / Allografts / Antigens, CD19 - immunology / Bacterial infections / CAR‐T cells / CD19 antigen / Cell therapy / Chemotherapy / Chronic lymphocytic leukemia / Europe / Female / Humans / Immunotherapy, Adoptive - adverse effects / Immunotherapy, Adoptive - methods / Kinases / Leukemia / Leukemia, Lymphocytic, Chronic, B-Cell - immunology / Leukemia, Lymphocytic, Chronic, B-Cell - mortality / Leukemia, Lymphocytic, Chronic, B-Cell - pathology / Leukemia, Lymphocytic, Chronic, B-Cell - therapy / Lymphoma / Lymphoma, Large B-Cell, Diffuse - pathology / Lymphoma, Large B-Cell, Diffuse - therapy / Male / Medical prognosis / Middle Aged / Mortality / Patients / Receptors, Chimeric Antigen - immunology / Response rates / Retrospective Studies / Richter transformation / Stem cell transplantation / T-Lymphocytes - immunology / Toxicity / Treatment Outcome