TY - JOUR
T1 - CD19 CAR T-Cell Therapy in Richter Transformation
T2 - A Multicentre Retrospective Analysis by the European Research Initiative on Chronic Lymphocytic Leukaemia
AU - Beyar-Katz, Ofrat
AU - Benjamini, Ohad
AU - Delgado, Julio
AU - Ruella, Marco
AU - Ram, Ron
AU - Grisariu, Sigal
AU - Visentin, Andrea
AU - Vandenberghe, Elisabeth
AU - Gentile, Massimo
AU - Avigdor, Abraham
AU - Shimoni, Avichai
AU - Shouval, Roni
AU - Marcus, Ronit
AU - Schuster, Stephen J.
AU - Ortiz-Maldonado, Valentin
AU - Ghilardi, Guido
AU - Paruzzo, Luca
AU - Zuckerman, Tsila
AU - Tadmor, Tamar
AU - Fineman, Riva
AU - Amit, Odelia
AU - Martinez-Cibrian, Nuria
AU - Gabrielli, Giulia
AU - Avni, Batia
AU - Minga, Eva
AU - Shem-Tov, Noga
AU - Scarfo, Lydia
AU - Yerushalmi, Ronit
AU - Nagler, Arnon
AU - Leiba, Ronit
AU - Danylesko, Ivetta
AU - Stamatopoulos, Kostas
AU - Chatzikonstantinou, Thomas
AU - Ghia, Paolo
AU - Herishanu, Yair
N1 - Publisher Copyright:
© 2025 The Author(s). Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.
PY - 2025/10
Y1 - 2025/10
N2 - 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.
AB - 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.
KW - CAR-T cells
KW - Richter transformation
KW - allogeneic SCT
UR - https://www.scopus.com/pages/publications/105019528036
U2 - 10.1111/jcmm.70841
DO - 10.1111/jcmm.70841
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C2 - 41123167
AN - SCOPUS:105019528036
SN - 1582-1838
VL - 29
JO - Journal of Cellular and Molecular Medicine
JF - Journal of Cellular and Molecular Medicine
IS - 20
M1 - e70841
ER -