Glofitamab penetrates the BBB and induces responses in patients with secondary CNS lymphoma. (A) Bar graph demonstrating the concentration of glofitamab in patient (Pt)–derived samples from the CSF and plasma. The relative proportion of glofitamab in the CSF compared with the plasma is listed as a percentage within the stacked bars for patients with synchronous CSF and plasma collections. (B) Induction of T-cell activation by the CSF of glofitamab-treated patient samples, as assessed by CD25 and CD69 upregulation. Peripheral blood T cells from a healthy donor were incubated for 24 hours with patient-derived CSF or buffer control solution in the presence of the CD20⁺ lymphoma cell line, Raji, at a 5:1 effector/target ratio. T cells incubated with glofitamab (0.1 μg/mL) and Raji served as a positive control. ∗∗∗P < .001. (C) T-cell cytotoxicity of CD20⁺ lymphoma cells induced by the CSF from glofitamab-treated patients. Peripheral blood T cells from a healthy donor were incubated for 24 hours with patient-derived CSF or buffer control solution in the presence of the CD20⁺ lymphoma cell line, Raji, at a 5:1 effector/target ratio. The extent of cytotoxicity was assessed by live/dead flow cytometric staining and was compared with conditions lacking T cells. Karpas-299, a CD20-negative lymphoma cell line, was used as a negative control. Raji incubated with T cells and glofitamab (0.1 μg/mL) served as a positive control. ∗∗∗P < .001. (D) Serial brain magnetic resonance imaging (MRI) scans from patient 1 with CNS lymphoma before (left panel), after 2 months (middle panel), and after 4 months (right panel) of glofitamab monotherapy. Imaging shows a near-complete response to treatment with a significant decrease in size and contrast enhancement within the CNS lesion (arrows) on T1-weighted postgadolinium contrast axial images. CxDx, cycle and day of glofitamab treatment; ns, not significant.