Psychiatric, cognitive, psychosocial, and neurological outcomes of chimeric antigen receptor T-cell therapy: protocol for a prospective study

BackgroundImmune effector cell-associated neurotoxicity syndrome (ICANS) is a common side-effect of chimeric antigen receptor T-cell (CAR-T) therapy, with symptoms ranging from mild to occasionally life-threatening. The psychiatric, cognitive, psychosocial, and neurological sequalae of ICANS are diverse and not well-specified, posing a challenge for diagnosis and management. The recovery trajectory of the syndrome is uncertain. Psychiatric, cognitive, psychosocial, and neurological status is rarely examined in this population pre-therapy, adding a layer of complexity to specifying symptoms pertinent solely to CAR-T treatment. AimsThe aim is to investigate psychiatric, cognitive, psychosocial, and neurological outcomes in patients after CAR-T therapy, particularly among those who develop ICANS. The project will establish a comprehensive pre-treatment baseline and will longitudinally monitor for therapy-associated change. MethodsA prospective longitudinal study of all adult patients in a single Australian haematology service undergoing CAR-T therapy. Neuropsychological and neurological examinations occur prior to CAR-T, and patients are reviewed during the acute post-treatment period, 28 days, 6 months, and 12 months post-infusion. Data will be sourced from objective psychometric measures, clinical examinations, self-report questionnaires, and accounts of subjective cognitive complaint to capture a broad spectrum of dysfunction and its daily functional impact. ConclusionsWe present a protocol of a research study that will describe the neurocognitive features specific to ICANS, characterise the underlying syndrome, identify predictors of differential post-infusion outcomes, and contribute to optimising the overall management of CAR-T patients. The protocol will serve as the basis of guidance regarding clinical and paraclinical follow-up of patients undergoing CAR-T cell therapy.