Abstract Details

We report our experiences from a total of 45 consecutive CAR T-cell transfusions in patients with active primary or secondary CNS lymphoma at the Massachusetts General Hospital. This cohort includes 17 patients treated for primary CNS lymphoma (PCNSL; one patient with two CAR T-cell transfusions) and 27 patients treated for secondary CNS lymphoma (SCNSL). Mild neurotoxicity (grade 1-2) was observed after 19/45 transfusions (42.2%) and severe neurotoxicity (grade 3-4) after 7/45 transfusions (15.6%). A larger increase in C-reactive protein (CRP) levels and higher rates of neurotoxicity were detected in SCNSL. Early fever and baseline CRP levels predicted neurotoxicity occurrence. CNS response was seen in 31 cases (68.9%), including complete responses of CNS disease in 18 cases (40.0%), lasting for a median of 11.4 ± 4.5 months. 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 a favorable CNS-progression free survival (5 versus 1 month, HR 0.28, CI 0.1-0.7; p = 0.010).

CD19-directed CAR T-cells exhibit promising anti-tumor effects and a favorable safety profile in patients with primary and secondary CNS lymphoma. Further evaluation on the optimal bridging regimens prior to CAR-T cells and corticosteroid use is warranted.