Chronic inflammatory demyelinating polyneuropathy (CIDP) after cilta-cel therapy

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.