Extended Data Fig. 3: Clinical imaging of CART-associated immune-related adverse events (CirAE) and colon biopsy results in patients who developed immune effector cell-associated enterocolitis.

(a) Clinical imaging of post-BCMA-CART CirAE: Cilta-cel#21: Magnetic resonance imaging (MRI) of the head and orbits illustrates enhancement within the left orbital apex extending to the left superior orbital fissure. There is thickening and edema in the left prechiasmatic optic nerve and left optic chiasm and enhancement within and along the left intraorbital, intracanalicular, and prechiasmatic optic nerve/sheath complex, consistent with optic neuritis. Chimeric antigen receptor (CAR) transgene was detectable at 59596 copies/µg gDNA in the cerebrospinal fluid (CSF). Cilta-cel#14: MRI of the head shows a rim-enhancing lesion in bilateral medial thalami extending to the hypothalamus measuring approximately 2.8 ×2.7 ×2.2 cm, with surrounding FLAIR signal abnormality extending bilaterally into the surrounding thalami, gangliocapsular regions, mammillary bodies, left greater than right midbrain, and optic chiasm. Ide-cel#1: CT chest showing multifocal tree-in-bud ground-glass opacities consistent with pneumonitis. Cilta-cel#4: endoscopy revealed many non-bleeding, cratered duodenal ulcers, and erosions without stigmata of bleeding beyond the second portion of the duodenum. Colonoscopy did not show any areas of ulcerations or erosions within the terminal ileum and colon. (b) H&E shows duodenal mucosa with graft-versus-host and Celiac disease-like patterns of injury, changes compatible with treatment (ciltacabtagene autoleucel) effects, and mild acute inflammation. Circle highlights villous atrophy and crypt hyperplasia. Arrow highlights prominent crypt apoptosis. RNAscope shows CART infiltration. BCMA was not detected. Representative micrographs from a single experiment; imaging was performed once and not independently replicated due to limited available tissue. (c) H&E shows colonic mucosa with mild crypt architectural distortion and markedly reduced plasma cells in the lamina propria. RNAscope shows CART infiltration. BCMA was not detected. Circle highlights a paucity of plasma cells in the lamina propria, resembling histologic features observed in common variable immunodeficiency. Representative micrographs from a single experiment; imaging was performed once and not independently replicated due to limited available tissue. BCMA: B-cell maturation antigen; CART: chimeric antigen receptor T-cell; Cy5: cyanine 5; FITC: fluorescein isothiocyanate; MRI: magnetic resonance imaging.