Real-World Incidence and Management of Non-Immune Effector Cell-Associated Neurotoxicity Syndrome Neurologic Events Following Ciltacabtagene Autoleucel in Multiple Myeloma.

Ciltacabtagene autoleucel (cilta-cel) is a chimeric antigen receptor T-cell (CAR-T) therapy for relapsed/refractory multiple myeloma (RRMM) approved after 1 prior line of therapy (LOT). Non-immune effector cell-associated neurotoxicity syndrome (ICANS) neurologic events (NEs) may occur following infusion. This real-world study evaluated non-ICANS NE onset and management among patients with RRMM treated with cilta-cel. Electronic medical records from Loopback Analytics (02/2022-05/2025) were used, supplemented with physician notes. Adults treated with cilta-cel after 1-3 and ≥4 prior LOT were included (N=171). New-onset non-ICANS NEs included cranial nerve palsy (CNP), parkinsonism, and Guillain-Barré syndrome. Clinical outcomes among these patients were described. Among 171 patients, 73 had 1-3 prior LOT and 98 had ≥4 prior LOT. Among patients with 1-3 prior LOT (median follow-up: 6.1 months), CNP occurred in 4 patients, while no parkinsonism or Guillain-Barré syndrome were observed. Following CNP onset, symptoms improved among 3 patients. Among patients with ≥4 prior LOT (median follow-up: 17.4 months), CNP occurred in 3 patients, while parkinsonism and Guillain-Barré syndrome each occurred in 1 patient. All patients with CNP had symptom improvement and the patient with Guillain-Barré syndrome had symptom resolution. Median peak ALC (103 cells/µL) was higher in patients with versus without non-ICANS NEs (1-3 prior LOT: 7.60 vs 2.12; ≥4 prior LOT: 11.64 vs 1.96). All patients with events had at least a partial response to cilta-cel and remained alive at the end of follow-up. This real-world cohort showed low incidence of CNP, parkinsonism, and Guillain-Barré syndrome following cilta-cel. Elevated post-infusion ALC warrants further investigation into its role as a biomarker to inform monitoring and management strategies, consistent with prior reports. Most patients with CNP reported improvement, the patient with Guillain-Barré syndrome reported resolution, all patients with available response assessments responded to cilta-cel, and no deaths were reported.