Toxicities and outcome after BCMA-directed CAR T-cell therapy for multiple myeloma. (A) Kinetics of neurotoxicity (ICANS) in each patient through 90 days after transfusion of BCMA-directed CAR T cells. Patients with mild ICANS (n = 25) and severe ICANS (n = 6) are depictured. Each row represents 1 patient, and the highest grade (Gr) of ICANS recorded on each day is color coded. Mean time to first fever of ≥38°C for patients with grade 1-2 ICANS (yellow dotted line) and grade 3-4 ICANS is indicated (red dotted line). The specific CAR T-cell product for each patient is also given. (B) Median ratio of the serum levels of the acute-phase proteins, C-reactive protein and ferritin, in relationship to serum levels at CAR T-cell transfusion. (C) Number of patients with each grade of CRS and ICANS. (D) Serum levels of albumin at CAR T-cell transfusion (left) and receiver operating characteristic curve for the prediction of ICANS of any grade by the serum levels of albumin (right). (E) Axial brain magnetic resonance imaging (MRI) with fluid-attenuated inversion recovery (FLAIR; left panel each) and diffusion-weighted imaging (DWI) sequences (middle panel) of the patients with parkinsonism-like features after CAR T-cell transfusion. No specific acute MRI abnormalities are detected in either patient. On [¹⁸F]FDG-PET imaging (right panel each), basal ganglion hypometabolism (arrows) is demonstrated in 1 patient (patient #30) whereas the other individual shows frontal hypometabolism (arrowheads). (F) Distribution of best disease response in patients with and without ICANS. (G) Kaplan-Meier estimates of overall survival after CAR T-cell transfusion for patients with (blue; n = 31) and without (gray; n = 45) ICANS. Points indicate patients who were deceased or censored, light shading indicates standard error of the mean. mOS, median overall survival.