Abstract
•Anti-CD19 CAR-T is an effective therapeutic modality for patients with relapsed Richter transformation that is refractory to currently available treatments.•With an encouraging ORR of 71%, and CR rates of 57%, 2-year PFS and OS were 32.5% (95%CI, 24.2 - 41.4) and 46.6% (95%CI, 37.7–55.7), respectively.•High rates of cumulative incidence of relapse noted at 2 years is a concern that needs further attention. Follow up studies will inform long term durability of responses.
Relapsed and/or refractory Richter transformation (RT) is generally associated with poor response to available therapies and 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 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:1-8), 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 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: 1.8-61.5) from CAR-T infusion, 2-year progression-free and overall survival were 32.5% (95%CI, 24-41) and 46.6% (95%CI, 38–58), respectively. The 2-year cumulative incidence of relapse and non-relapse mortality were 58.8% (95% CI, 50 – 67), and 8.7% (95% CI, 4 – 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.