Chimeric Antigen Receptor T-Cell Therapy for Richter Transformation: A CIBMTR Analysis

Relapsed and/or refractory Richter transformation (RT) is generally associated with poor response to available therapies and a short survival time. As RT patients were excluded from participating in the pivotal studies of chimeric antigen receptor T cell therapy (CAR-T) for large B-cell lymphoma, there is a paucity of information about the efficacy of CAR-T in RT. Therefore, through the Center for International Blood and Marrow Transplant Research (CIBMTR) registry, we analyzed data from 140 RT patients who received anti-CD19 CAR-T between 2018 and 2023. Patients had received a median of 3 lines of therapy for RT (range: 1 to 8), with nearly 43% being exposed to a Bruton's tyrosine kinase inhibitor and/or venetoclax. Axicabtagene ciloleucel (axi-cel) (65%) and tisagenlecleucel (tisa-cel) (28%) were the most commonly prescribed products. Grade ≥3 cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome occurred in 9.4% and 20%, respectively. After a median follow-up of 25 months (range: 1.8 to 61.5) from CAR-T infusion, 2-year progression-free and overall survival were 32.5% (95% CI, 24 to 41) and 46.6% (95% CI, 38 to 58), respectively. The 2-year cumulative incidence of relapse and non-relapse mortality were 58.8% (95% CI, 50 to 67), and 8.7% (95% CI, 4% to 14%), respectively. Poor performance status and refractory disease before CAR-T infusion were predictive of inferior survival and disease progression. Our results show that anti-CD19 CAR-T can function as an effective treatment modality for a proportion of RT patients.