Disease-specific outcomes after chimeric antigen receptor T-cell therapy

We compared outcomes of patients with B-cell malignancies treated in clinical trials with the same CD19 chimeric antigen receptor (CAR) T-cells across different indications, including B-cell acute lymphoblastic leukaemia (B-ALL), diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma (MCL) and follicular lymphoma (FL). We found that for a given CAR T-cell, efficacy and toxicity varied depending on the disease. Overall, we found a low rate of primary resistance in FL, MCL and B-ALL compared with DLBCL. Acute toxicities (cytokine release syndrome and ICANS) appeared to be significantly less severe in FL compared with more aggressive diseases, such as B-ALL, DLBCL and MCL. These observations suggest that each B-cell malignancy harbours specific biology, which may interact differently with CAR T-cell therapy. Thus, CAR T-cells may be tailored differently depending on the type of B-cell malignancy to optimise their efficacy and safety.