Purpose: 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. Patients and Methods: 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. Results: 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 (10 3 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. Conclusion: 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. An infographic titled Real-World Incidence and Management of Non-ICANS Neurologic Events Following Ciltacabtagene Autoleucel in Multiple Myeloma. Subtitle: Retrospective EMR cohort study evaluating the incidence, clinical characteristics, management and outcomes of non-ICANS NEs following cilta-cel in patients with MM treated after 1– 3 prior LOT or 4 prior LOT. Left section, RESULTS and PATIENT CHARACTERISTICS with a patient icon group: 171 patients with MM treated with cilta-cel after 1– 3 prior LOT (n equals 73) or 4 prior LOT (n equals 98). BASELINE DEMOGRAPHICS table: No. of patients 73 and 98; Median age 65 y and 64 y; Female 46.6 percent and 37.8 percent. CLINICAL CHARACTERISTICS: High-risk cytogenetic abnormalities 55.8 percent and 63.3 percent; Median follow-up 6.1 months and 17.4 months. Middle section, a left-to-right timeline with markers: Day 0 Cilta-cel infusion; Day 11 Median Peak ALC; Days 18– 105 Onset of non-ICANS NEs. Below the timeline, a bar chart labeled MEDIAN PEAK ALC (10 superscript 3 cells per microliter). For 1– 3 prior LOT: 7.60 for patients who developed non-ICANS NEs and 2.12 for patients who did not develop non-ICANS NEs. For 4 prior LOT: 11.64 for patients who developed non-ICANS NEs and 1.96 for patients who did not develop non-ICANS NEs. Right-middle section, RATE AND TIME OF ONSET OF NON-ICANS NEs with two columns (1– 3 prior LOT and 4 prior LOT): Cranial nerve palsy (Onset days 18– 37) 5.5 percent (n equals 4) and 3.1 percent (n equals 3). Parkinsonism (Onset day 46) 0.0 percent and 1.0 percent (n equals 1). Guillain–Barré syndrome (Onset day 105) 0.0 percent and 1.0 percent (n equals 1). Right section, MANAGEMENT STRATEGIES with treatment icons and a list under MANAGED WITH: Cyclophosphamide; Dexamethasone or Prednisone; Intravenous immunoglobulin; Plasma cell exchange; Valacyclovir. Far-right section, OUTCOMES with a target icon and donut charts under IMPROVEMENT IN CRANIAL NERVE PALSY: 1– 3 prior LOT 75 percent; 4 prior LOT 100 percent. Notes: All with available response assessments responded to cilta-cel. In the 1 patient with Guillain–Barré syndrome, symptom resolution occurred. 1 patient experienced disease progression. No deaths were reported. Bottom callout with a lightbulb icon: The incidence of non-ICANS NEs was low following cilta-cel, both in patients with 1– 3 and 4 prior LOT. Elevated post-infusion ALC warrants further investigation into its role as a biomarker to inform monitoring and management strategies. Most patients reported an improvement in cranial nerve palsy and symptoms resolved in the 1 patient with Guillain–Barré syndrome. All evaluable patients responded to cilta-cel and no deaths were reported.Infographic on low non-ICANS neurologic event rates, timing, management and outcomes after cilta-cel. Keywords: absolute lymphocyte count, CAR-T, cranial nerve palsy, Guillain-Barré syndrome, management strategy, parkinsonism
Hansen et al. (Fri,) studied this question.