Mid-term neurocognitive outcomes after CAR T cell therapy in central nervous system lymphomas: statistical analysis plan

Background: Chimeric antigen receptor (CAR) T cells are an innovative therapeutic option for hematological malignancies. The indications of anti-CD19 CAR T cells have recently been extended to the treatment of central nervous system lymphomas. They can cause an immune effector cell-associated neurotoxicity syndrome, which has been reported with similar rates and short-term prognosis in central nervous system and systemic lymphomas. However, longer-term neurocognitive outcomes in central nervous system lymphomas after treatment with CAR T cells remain unknown. Clarifying them is especially important because of the frequent pre-existing cognitive impairment in these patients, which could theoretically either worsen or improve after treatment. This study therefore aims to characterize mid-term neurocognitive outcomes following CAR T cell therapy in central nervous system lymphomas.Methods: In this study, demographic, clinical, and neurocognitive longitudinal data about patients treated with anti-CD19 CAR T cells for a central nervous system lymphoma will be retrospectively collected from the French LOC network database. The primary outcome will be the change in Montreal cognitive assessment scores between baseline and 12 months post-treatment. The data analysis framework will include paired Student’s t-tests and linear regression models, as well as more advanced methods such as factor analysis, iterative principal component analysis, and trajectory modeling. Missing data will be managed by multiple imputation. The dataset will be synthesized in order to be released in an open version.Discussion: The proposed statistical framework, combining conventional analysis methods with more advanced machine learning techniques, has the potential to enhance the understanding of neurocognitive trajectories after CAR T cell therapy in central nervous system lymphomas. Identifying potentially distinct neurocognitive profiles and prognostic factors may inform both current clinical practice and further research into therapeutic options in this condition.