Beat pediatric ALL MRD: CD28 CAR T and transplant

Abstract

In this issue of Blood, Curran et al report clinical trial results evaluating a second-generation CD19-directed chimeric antigen receptor (CAR) T-cell therapy in pediatric and young adult (AYA) relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL). Autologous CAR T-cell immunotherapies are revolutionizing the treatment of B-cell malignancies. CAR T-cell treatment involves genetic engineering of a patient’s T cells by insertion of a CAR construct, which upon expression, recognizes CD19 on neoplastic cells and triggers T-cell activation and tumor killing. The paper is notable for several reasons. First, it confirms in a pediatric population the importance of intensive lymphodepletion before CAR T-cell infusion to achieve responses. Second, in children treated with a CD28-based CAR T cell achieving minimal residual disease (MRD)⁻ status, consolidative allogeneic transplant leads to acceptable long-term disease-free survival. Lastly, this report provides key additional clinical data on a CD28-based CART19 product whose commercial development was halted due to cerebral edema deaths during a separate pharma-sponsored trial.