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Background Chimeric Antigen Receptor T-cell (CAR-T) therapy has revolutionised the treatment of haematological malignancies. Despite its efficacy, CAR-T therapy is associated with a high burden of adverse effects including Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS). ICANS presents with a broad spectrum of neurological symptoms, yet the frequency of different neurological manifestations remains poorly characterised.Objectives This systematic review aims to: (1) determine the total proportion of reported ICANS cases across a range of populations and CAR-T products, (2) assess the variability in neurological presentation, and (3) evaluate symptom profiles and phenotypic subgroups of ICANS to enhance understanding of its clinical manifestations.Methods A systematic search of PubMed, EMBASE, Scopus, and Cochrane Library will be conducted for studies published between 1 January 2017 and 1 January 2025. Eligible studies included observational studies, clinical trials, and retrospective analyses that reported ICANS incidence, symptom profiles, and severity grading. Data were extracted on study characteristics, patient demographics, CAR-T cell constructs, and neurological symptoms. Risk of bias will be assessed and Meta-analyses where feasible, using random-effects models to pool estimates of ICANS incidence and symptom frequencies.Results Data extraction and analysis are ongoing.Conclusions This systematic review will provide comprehensive insights into the incidence, symptom patterns, and phenotypic variability of ICANS in CAR-T therapy.amber.corrigan1@nhs.net