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

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 l...

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Main Authors: Kaulen, Leon D. (Author) , Karschnia, Philipp (Author) , Doubrovinskaia, Sofia (Author) , Abramson, Jeremy S. (Author) , Martinez-Lage, Maria (Author) , Shankar, Ganesh (Author) , Choi, Bryan D. (Author) , Barnes, Jeffrey A. (Author) , El-Jawahri, Areej (Author) , Hochberg, Ephraim P. (Author) , Johnson, P. Connor (Author) , Soumerai, Jacob D. (Author) , Wick, Wolfgang (Author) , Maus, Marcela V. (Author) , Chen, Yi-Bin (Author) , Frigault, Matthew J. (Author) , Dietrich, Jorg (Author)
Format: Article (Journal)
Language:English
Published: 23 October 2024
In: American journal of hematology
Year: 2024, Volume: 99, Issue: 12, Pages: 2411-2415
ISSN:1096-8652
DOI:10.1002/ajh.27505
Online Access:Verlag, kostenfrei, Volltext: https://doi.org/10.1002/ajh.27505
Verlag, kostenfrei, Volltext: https://onlinelibrary.wiley.com/doi/abs/10.1002/ajh.27505
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Author Notes: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
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Summary: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.
Item Description:Gesehen am 12.05.2025
Physical Description:Online Resource
ISSN:1096-8652
DOI:10.1002/ajh.27505

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