2024 American Academy of Neurology Abstract Website

Jorg Dietrich¹, Isabel Arrillaga-Romany¹, April Eichler¹, Deborah Forst¹, Elizabeth Gerstner¹, Justin Jordan¹, Ina Ly¹, Scott Plotkin¹, Nancy Wang¹, Maria Martinez-Lage¹, Sebastian Friedrich Winter¹, Kai Rejeski³, Jorg-Christian Tonn⁴, Louisa vom Baumgarten⁴, Daniel Cahill¹, Brian Nahed¹, Ganesh Shankar², Jeremy Abramson¹, Jeffrey Barnes¹, Areej El-Jawahri¹, Ephraim Hochberg¹, Patrick Johnson¹, Jacob Soumerai¹, Ronald Takvorian¹, Yi-Bin Chen¹, Matthew Frigault¹, Philipp Karschnia⁴
¹Massachusetts General Hospital, Harvard Medical School, ²Neurosurgery, Massachusetts General Hospital, Harvard Medical School, ³Medicine, ⁴Neurosurgery, Ludwig Maximilian University

Objective:

To assess the efficacy and tolerability of CAR-T cells in primary and secondary CNS lymphoma.

Background:

Chimeric antigen receptor (CAR) T-cells targeting CD19 have been established as a leading T-cell therapy for systemic B-cell lymphomas; however, data for patients with CNS involvement from systemic disease or primary CNS lymphoma are limited.

Design/Methods:

Retrospective analysis of patients treated with CAR-T cells for primary and secondary CNS lymphoma. Clinical data, CNS-specific toxicities, imaging findings, and outcomes were analyzed.

Results:

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).

Conclusions:

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.