Journal Article (Letter)

DKFZ-2025-02181

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Chronic inflammatory demyelinating polyneuropathy (CIDP) after cilta-cel therapy.

Korenkov, M. ; Liebaert, J. ; Yousefian, S. ; Schwartz, C.DKFZ* ; Demel, U. M. ; Braune, J. ; Odabasi, M. C. ; Herzberg, L. ; Böckle, D. ; Görür, N. C. ; V Landenberg-Roberg, V. ; Bohl, S. ; Tregel, E. ; Hennig, S. ; Franke, C. ; Haas, S.DKFZ* ; Keller, U.DKFZ* ; Krönke, J.DKFZ* ; Busse, C.DKFZ*

2025
Springer Nature [London]

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Please use a persistent id in citations: doi:10.1038/s41408-025-01384-9

Abstract: Ciltacabtagene-autoleucel (cilta-cel) is a CAR-T cell therapy highly active in relapsed/refractory multiple myeloma but can induce severe immune-mediated toxicities. We describe two patients who developed chronic inflammatory demyelinating polyneuropathy (CIDP) after cilta-cel. Patient 1 presented with rapidly progressive gait ataxia, flaccid paraparesis, and oculomotor palsy 112 days post infusion; Patient 2 developed an analogous syndrome on day 19. In both patients, electromyography and nerve-conduction studies confirmed sensorimotor axonal-demyelinating neuropathy; brain MRI and CSF infection panels were unremarkable. CAR-T cells were detectable in blood and CSF, yet a predominance of CD8⁺ non-CAR-Tcells was observed. TCR-β sequencing revealed a hyper-expanded clone (~30% of all reads) in patient 1 versus a polyclonal repertoire in patient 2. High-dose dexamethasone plus intravenous immunoglobulin failed to improve neurologic symptoms and prompted T-cell-depleting cyclophosphamide, which lowered CAR- and non-CAR-T cells. Patient 1 died from respiratory failure, whereas patient 2 improved and could be discharged. These observations indicate that CIDP is a severe complication of cilta-cel therapy and may arise from bystander expansion of autoreactive CD8⁺ T-cells rather than direct CAR-T cell activity. Timely escalation to T-cell-depleting therapy may improve outcomes.

Keyword(s): Humans (MeSH) ; Polyradiculoneuropathy, Chronic Inflammatory Demyelinating: etiology (MeSH) ; Polyradiculoneuropathy, Chronic Inflammatory Demyelinating: diagnosis (MeSH) ; Male (MeSH) ; Middle Aged (MeSH) ; Immunotherapy, Adoptive: adverse effects (MeSH) ; Female (MeSH) ; Aged (MeSH)

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Contributing Institute(s):

1. DKTK Koordinierungsstelle Berlin (BE01)

Research Program(s):

1. 899 - ohne Topic (POF4-899) (POF4-899)

Appears in the scientific report 2025

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