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

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.