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Multicenter Study
. 2025 Oct;29(20):e70841.
doi: 10.1111/jcmm.70841.

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

Ofrat Beyar-Katz  1   2 , Ohad Benjamini  3   4 , Julio Delgado  5 , Marco Ruella  6   7 , Ron Ram  4   8 , Sigal Grisariu  9   10 , Andrea Visentin  11 , Elisabeth Vandenberghe  12   13 , Massimo Gentile  14   15 , Abraham Avigdor  3   4 , Avichai Shimoni  3   4 , Roni Shouval  16   17 , Ronit Marcus  3   4 , Stephen J Schuster  6   7 , Valentin Ortiz-Maldonado  5 , Guido Ghilardi  6   7 , Luca Paruzzo  6   7 , Tsila Zuckerman  1   2 , Tamar Tadmor  2   18 , Riva Fineman  1   2 , Odelia Amit  4   8 , Nuria Martinez-Cibrian  5 , Giulia Gabrielli  6   7 , Batia Avni  9   10 , Eva Minga  19 , Noga Shem-Tov  3   4 , Lydia Scarfo  20   21 , Ronit Yerushalmi  3   4 , Arnon Nagler  3   4 , Ronit Leiba  22 , Ivetta Danylesko  3   4 , Kostas Stamatopoulos  19   23 , Thomas Chatzikonstantinou  19 , Paolo Ghia  20   21 , Yair Herishanu  4   8
Affiliations
Multicenter Study

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

Ofrat Beyar-Katz et al. J Cell Mol Med. 2025 Oct.

Abstract

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.

Keywords: CAR‐T cells; Richter transformation; allogeneic SCT.

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Conflict of interest statement

O.B.‐K. and R.R.—Honorarium from novartis and gilead. M.R.—Vittoria Biotherapeutics: Current equity holder in private company, Patents and Royalties; AbClon Inc.: Other: Consultancy, Research Funding. S.G.—Gilead, Medison, MSD, Novartis, Sanofi, Takeda: Consultancy. A.V.—attended scientific advisory boards organised by Johnson & Johnson, Abbvie, Astrazeneca, BeiGene and Takeda; Speaker Bordeaux for Johnson & Johnson and Abbvie. A.A.—Karyospharm: Research Funding; Ascentage: Consultancy, Honoraria, Speakers Bureau; BeiGene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other, Speakers Bureau; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other, Research Funding, Speakers Bureau; Bristol Myers Squibb: Consultancy, Honoraria, Research Funding, Speakers Bureau; A0bbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other, Research Funding, Speakers Bureau; Eli Lilly: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other, Speakers Bureau; TG Therapeutics: Consultancy; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, accommodations, expenses, Research Funding, Speakers Bureau; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other, Research Funding, Speakers Bureau. V.O.‐M.—Pfizer: Honoraria; Kite/Gilead: Honoraria, Other: Travel grants; Miltenyi: Honoraria; Hospital Clínic de Barcelona: Current Employment; Janssen: Honoraria, Other: Travel grants; Celgene‐BMS: Honoraria, Other: Travel grants; Novartis: Honoraria. G.G.—Vittoria Biotherapeutics: Honoraria. B.A.—Sanofi: Consultancy; Johnson and Johnson: Consultancy; Novartis: Consultancy; MSD: Consultancy; Takeda: Consultancy; Medison: Consultancy. T.T.—Janssen, Roche, Abbvie, Astra, Takeda, Novartis, Beigene, Medison: Consultancy, Research Funding. L.S.—Janssen: Honoraria; Lilly: Honoraria; BeiGene: Honoraria; AstraZeneca: Honoraria; AbbVie: Honoraria; Octapharma: Honoraria. K.S.—AstraZeneca: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Novartis: Research Funding; Roche: Research Funding; Bristol Myers Squibb: Honoraria; AbbVie: Honoraria, Research Funding; Lilly: Honoraria. T.C.—Honoraria from AbbVie, AstraZeneca and BeiGene. P.G.—Loxo@Lilly: Consultancy; Galapagos: Consultancy; Johnson&Johnson: Consultancy, Research Funding; Bristol Myers Squibb: Consultancy, Research. unding; BeiGen: Consultancy; AstraZeneca: Consultancy, Research Funding; AbbvVie: Consultancy, Research Funding; MSD: Consultancy; Galapagos: Consultancy; Roche: Consultancy. O.B., J.D., E.V., M.G., A.S., R.S., R.M., S.J.S., L.P., T.Z., R.F., O.A., N.M.C., G.G., R.Y., A.N., R.L., I.D., E.M., N.S.‐T. declare no conflicts of interest.

Figures

FIGURE 1
FIGURE 1
Response rates to CAR T‐cells in RT patients. Response at 1 month and 3 months post CAR T‐cells.
FIGURE 2
FIGURE 2
Survival of all patients. (A) Progression‐free survival in patients with RT following CAR T‐cell infusion. (B) Overall survival in patients with RT following CAR T‐cell infusion.
FIGURE 3
FIGURE 3
Survival based on best response to CAR T‐cell therapy. (A) Progression‐free survival of patients achieving complete response (CR), partial response (PR) and progressive disease/stable disease (PD + SD). (B) Overall survival of patients achieving CR, PR and PD + SD.
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