Pola partially penetrates the BBB and pola-based treatment induces complete remissions in CNS lymphoma patients. (A) Bar graph demonstrating the concentration of pola (as measured by acMMAE) in Pt-derived CSF and plasma samples. Plasma and CSF acMMAE concentrations are listed within the green and blue stacked bars, respectively. The relative proportion of pola in the CSF compared to the plasma is listed as a percentage at the top of the stacked bars for patients with synchronous CSF and plasma collections. Pts with CNS lymphoma and systemic DLBCL are separately designated. (B) Serial positron emission tomography scan images from Pt 1 with CNS lymphoma before (left panels) and 2 months after (right panels) pola and intrathecal chemotherapy treatment. Black and white arrows indicate areas of active systemic and CNS disease before treatment, respectively. Top panels demonstrate global assessment of disease status before and after pola as assessed by maximum intensity projection, and the bottom panels show a representative hypermetabolic spinal cord tumor lesion before and after pola treatment. (C) Serial brain magnetic resonance imaging scans from Pt 2 with CNS lymphoma before (left panel) and 5 months after (right panel) treatment with pola and ibrutinib. Imaging shows a complete response to treatment with resolution of the large contrast-enhancing CNS lesion (arrow) on T1-weighted postgadolinium contrast axial images. CxDx, cycle and day of pola treatment; N/A, not applicable; Pt, patient.