Retrospective single-center study of 117 consecutive adults receiving in-label cilta-cel for relapsed/refractory multiple myeloma (May 2023–December 2025; median age 69, median follow-up 11.3 months), characterizing the clinical spectrum, management, and outcomes of severe non-ICANS IEC neurotoxicity and proposing a structured neurology–oncology co-management framework.
10/117 patients (8.5%) developed severe non-ICANS IEC neurotoxicity at a median of 45 days post-infusion (range 11–160 days). All 3 IEC-GBS cases were fatal (CTCAE Grade 5); 2/3 IEC-PKS patients died from infectious complications after immunosuppression. Non-relapse mortality was 50% in the neurotoxicity group vs. 8.4% in controls; median survival was 8.1 months vs. not reached (log-rank P <0.001). Peak CAR-T copies were significantly higher in neurotoxicity patients (median 710,766 vs. 131,077 copies/10⁶ leukocytes; P <0.001), and 9/10 had an ALCpeak >3 ×10⁹/L.
Retrospective single-center design with small subgroup sizes; management was non-standardized and confounded by syndrome severity, precluding causal inference; short follow-up and censoring limit survival comparisons.
Monitor all cilta-cel patients beyond Day 30 for new neurologic symptoms — IEC-GBS, IEC-PKS, cranial nerve palsies, and encephalitis can emerge weeks to months post-infusion and carry high mortality. An ALCpeak >3 ×10⁹/L signals elevated risk and should trigger heightened neurologic surveillance; early neurology co-management and a structured triage protocol are recommended for any new neurologic deficit after CAR-T infusion.
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