دورية أكاديمية
Neurotoxicity and management of primary and secondary central nervous system lymphoma after adoptive immunotherapy with CD19-directed chimeric antigen receptor T-cells
| العنوان: | Neurotoxicity and management of primary and secondary central nervous system lymphoma after adoptive immunotherapy with CD19-directed chimeric antigen receptor T-cells |
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| المؤلفون: | Karschnia, Philipp, Arrillaga-Romany, Isabel C, Eichler, April, Forst, Deborah A, Gerstner, Elizabeth, Jordan, Justin T, Ly, Ina, Plotkin, Scott R, Wang, Nancy, Martinez-Lage, Maria, Winter, Sebastian F, Tonn, Joerg-Christian, Rejeski, Kai, von Baumgarten, Louisa, Cahill, Daniel P, Nahed, Brian V, Shankar, Ganesh M, Abramson, Jeremy S, Barnes, Jeffrey A, El-Jawahri, Areej, Hochberg, Ephraim P, Johnson, P Connor, Soumerai, Jacob D, Takvorian, Ronald W, Chen, Yi-Bin, Frigault, Matthew J, Dietrich, Jorg |
| المصدر: | Neuro-Oncology ; volume 25, issue 12, page 2239-2249 ; ISSN 1522-8517 1523-5866 |
| بيانات النشر: | Oxford University Press (OUP) |
| سنة النشر: | 2023 |
| مصطلحات موضوعية: | Cancer Research, Neurology (clinical), Oncology |
| الوصف: | Background Chimeric antigen receptor (CAR) T-cells targeting CD19 have been established as a leading engineered T-cell therapy for B-cell lymphomas; however, data for patients with central nervous system (CNS) involvement are limited. 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 5-year period. Results Our cohort includes 17 patients with primary CNS lymphoma (PCNSL; 1 patient with 2 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 immune effector cell-associated neurotoxicity syndrome (ICANS) (grade 3–4) after 7/45 transfusions (15.6%). 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. Dexamethasone dose at time of lymphodepletion (but not at or after CAR T-cell transfusion) was associated with an increased risk for CNS progression (hazard ratios [HR] per mg/d: 1.16, P = .031). If bridging therapy was warranted, the use of ibrutinib translated into favorable CNS-progression-free survival (5 vs. 1 month, HR 0.28, CI 0.1–0.7; P = .010). Conclusions CAR T-cells exhibit promising antitumor effects and a favorable safety profile in CNS lymphoma. Further evaluation of the role of bridging regimens and corticosteroids is warranted. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1093/neuonc/noad118 |
| DOI: | 10.1093/neuonc/noad118/51040930/noad118.pdf |
| الإتاحة: | https://doi.org/10.1093/neuonc/noad118Test https://academic.oup.com/neuro-oncology/article-pdf/25/12/2239/54126531/noad118.pdfTest |
| حقوق: | https://academic.oup.com/pages/standard-publication-reuse-rightsTest |
| رقم الانضمام: | edsbas.1C032483 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1093/neuonc/noad118 |
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