Toxicities and outcome after CD19-directed chimeric antigen receptor T-cell therapy for secondary neurolymphomatosis

• Verfasst von: Kaulen, Leon D. [VerfasserIn]
• Verfasst von: Karschnia, Philipp [VerfasserIn]
• Verfasst von: Doubrovinskaia, Sofia [VerfasserIn]
• Verfasst von: Abramson, Jeremy S. [VerfasserIn]
• Verfasst von: Martinez-Lage, Maria [VerfasserIn]
• Verfasst von: Shankar, Ganesh [VerfasserIn]
• Verfasst von: Choi, Bryan D. [VerfasserIn]
• Verfasst von: Barnes, Jeffrey A. [VerfasserIn]
• Verfasst von: El-Jawahri, Areej [VerfasserIn]
• Verfasst von: Hochberg, Ephraim P. [VerfasserIn]
• Verfasst von: Johnson, P. Connor [VerfasserIn]
• Verfasst von: Soumerai, Jacob D. [VerfasserIn]
• Verfasst von: Wick, Wolfgang [VerfasserIn]
• Verfasst von: Maus, Marcela V. [VerfasserIn]
• Verfasst von: Chen, Yi-Bin [VerfasserIn]
• Verfasst von: Frigault, Matthew J. [VerfasserIn]
• Verfasst von: Dietrich, Jorg [VerfasserIn]
• Titel: Toxicities and outcome after CD19-directed chimeric antigen receptor T-cell therapy for secondary neurolymphomatosis
• Verf.angabe: Leon D. Kaulen, Philipp Karschnia, Sofia Doubrovinskaia, Jeremy S. Abramson, Maria Martinez-Lage, Ganesh Shankar, Bryan D. Choi, Jeffrey A. Barnes, Areej El-Jawahri, Ephraim P. Hochberg, P. Connor Johnson, Jacob D. Soumerai, Wolfgang Wick, Marcela V. Maus, Yi-Bin Chen, Matthew J. Frigault, Jorg Dietrich
• E-Jahr: 2024
• Jahr: 23 October 2024
• Umfang: 5 S.
• Illustrationen: Illustrationen
• Fussnoten: Gesehen am 12.05.2025
• Titel Quelle: Enthalten in: American journal of hematology
• Ort Quelle: New York, NY : Wiley-Liss, 1976
• Jahr Quelle: 2024
• Band/Heft Quelle: 99(2024), 12 vom: Dez., Seite 2411-2415
• ISSN Quelle: 1096-8652
• DOI: doi:10.1002/ajh.27505
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1925428419

Abstract

Lymphomatous infiltration of the peripheral nervous system (PNS), termed neurolymphomatosis, represents a distinct extranodal non-Hodgkin lymphoma variant with dismal outcome. CD19-directed chimeric antigen receptor (CD19-CAR) T-cell therapy has emerged as a safe and effective treatment for B-cell lymphomas. We aimed to assess toxicity and efficacy of CD19-CAR T-cells in neurolymphomatosis. Neurolymphomatosis patients treated with CD19 CAR T-cells were retrospectively identified at Massachusetts General Hospital over a six-year period. Toxicities were graded according to the ASTCT classification, management, and response rates were recorded. Eleven neurolymphomatosis patients were identified with a median of 2 lines of PNS-directed treatments (range: 1-3) prior to receiving CD19-CAR T-cells. Neurolymphomatosis localized to the nerve roots (8/11, 73%), plexus (5/11, 45%), peripheral (4/11, 36%) and cranial nerves (5/11, 45%). Low grade cytokine release syndrome (CRS) was detected in 8/11 (73%; grade 1: N = 7; grade 2: N = 1) cases. Low- and high-grade immune cell-associated neurotoxicity syndrome (ICANS) were recorded in 5/11 (45%; grade 1: N = 4; grade 2: N = 1) and 1/11 (9%; grade 4) patients, respectively. CRP levels at infusion were predictive of ICANS (area under the curve: 0.96, p = 0.01). Seven of eleven neurolymphomatosis patients (64%) responded to CD19-CAR T-cells. Complete remissions (CR) were achieved in three cases (27%), with 2 patients in sustained CR nine and 46 months after CD19-CAR infusion. Median progression-free survival (PFS) was 4 months. Collectively, CD19-CAR T-cell treatment was well tolerated and showed promising efficacy in recurrent neurolymphomatosis, a difficult to treat condition with unmet medical need. Findings suggest that CD19-CAR may sufficiently penetrate the blood-nerve barrier. Toxicity and outcomes were overall similar to CAR-T cell therapy in CNS lymphoma.