多发性骨髓瘤中 Ciltacabtagene Autoleucel 治疗后非免疫效应细胞相关神经毒性综合征神经系统事件的真实世界发生率和处理

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-Barr 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-Barr 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-Barr syndrome each occurred in 1 patient. All patients with CNP had symptom improvement and the patient with Guillain-Barr syndrome had symptom resolution. Median peak ALC (10 3 cells/ L) 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-Barr 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-Barr syndrome reported resolution, all patients with available response assessments responded to cilta-cel, and no deaths were reported.