CTIM-38. NEUROTOXICITY AND MANAGEMENT OF PRIMARY AND SECONDARY CNS LYMPHOMA AFTER ADOPTIVE IMMUNOTHERAPY WITH CD19-DIRECTED CAR T-CELLS

Abstract BACKGROUND Chimeric antigen receptor (CAR) T-cells targeting CD19 have been established as a leading engineered T-cell therapy for systemic B-cell lymphomas; however, efficacy data for patients with CNS involvement are limited. Also, there are concerns about increased neurotoxicities (denoted by the term 'ICANS') when the target antigen is present within the CNS. METHODS We retrospectively report on CNS-specific toxicities, management, and CNS response of 45 consecutive CAR T-cell transfusions for patients with active CNS lymphoma at the Massachusetts General Hospital over a five-year period. RESULTS Our cohort includes 17 patients with primary CNS lymphoma (PCNSL; one patient with two CAR T-cell transfusions) and 27 patients with secondary CNS lymphoma (SCNSL). Mild ICANS (grade 1-2) was observed after 19/45 transfusions (42.2%) and severe ICANS (grade 3-4) after 7/45 transfusions (15.6%). No fatalities were directly attributed to ICANS. A larger increase in C-reactive protein (CRP) levels and higher rates of ICANS were detected in SCNSL. Early fever and baseline C-reactive protein levels were associated with ICANS occurrence. CNS response was seen in 31 cases (68.9%), including a complete response of CNS disease in 18 cases (40.0%) which lasted for a median of 11.4 ± 4.5 months. Similar response rates were seen in both patients with parenchymal and leptomeningeal involvement. Dexamethasone dose at time of lymphodepletion (but not at or after CAR T-cell transfusion) was associated with an increased risk for CNS progression (HR per mg/d: 1.16, p = 0.031). If bridging therapy was warranted, the use of ibrutinib translated into favourable CNS-progression free survival (5 versus 1 month, HR 0.28, CI 0.1-0.7; p = 0.010). CONCLUSION CAR T-cells exhibit promising anti-tumor effects and a favourable safety profile in CNS lymphoma. Further evaluation of the role of bridging regimens and corticosteroids is warranted to boost the success of such therapy.