ARI-0001 CAR-T therapy for R/R CLL and Richter’s syndrome

Valentín Ortiz-Maldonado, MD, Hospital Clínic de Barcelona, Barcelona, Spain, comments on the use of chimeric antigen receptor T-cells (CAR-T) in relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL). Patients who fail to ibrutinib or venetoclax and also have a high-risk genetic profile such as TP53 mutations or complex karyotype have worse outcomes with tailored CAR T-cell therapy than other malignancies treated with standard CAR-T. Toxicity results of experimental ARI-0001 in 8 R/R patients with CLL/Richter’s transformation showed CRS in 87%, severe in 12% of cases, and 37% required tocilizumab, but no cases of immune effector cell-associated neurotoxicity syndrome (ICANS) were observed. Efficacy results show 100% measurable residual disease (MRD)-negative complete response (CR) for the CLL component and 60% non-relapse complete metabolic responders for Richter transformation, opening the perspectives for CAR-T treatment for these groups of patients. This interview took place at the 48th Annual Meeting of the European Group for Blood and Marrow Transplantation (EBMT) 2022, which was held virtually.