CAR-T cell therapy: practical guide to routine laboratory monitoring

Chimeric antigen receptor (CAR)-T cell therapy is a genetically-modified cellular immunotherapy that has a current established role in the treatment of relapsed/refractory B-cell acute lymphoblastic leukaemia and diffuse large B-cell lymphoma, with emerging utility in a spectrum of other haematological and solid organ malignancies. It is associated with a number of characteristic toxicities, most notably cytokine release syndrome and neurotoxicity, for which laboratory testing can aid in the prediction of severity and in monitoring. Other toxicities, such as cytopenias/marrow hypoplasia, hypogammagloblinaemia and delayed immune reconstitution are recognised and require monitoring due to the implications for infection risk and prophylaxis. The detection or quantitation of circulating CAR-T can be clinically useful, and is achieved through both direct methods, if available, or indirect/surrogate methods. It is important that the laboratory is informed of the CAR-T therapy and target antigen whenever tissue is collected, both for response assessment and investigation of possible relapse, so that the expression of the relevant antigen can be assessed, in order to distinguish antigen-positive and -negative relapses. Finally, the measurement of circulating tumour DNA has an evolving role in the surveillance of malignancy, with evidence of its utility in the post-CAR-T setting, including predicting patients who will inevitably experience frank relapse, potentially allowing for pre-emptive therapy.