Clinical course, risk factors and mitigating strategies for Immune effector cell-associated late onset neurotoxicities after ciltacabtagene autoleucel CAR-T in multiple myeloma

We examined the clinical course and risk factors for late onset neurotoxicities, including nerve palsies (IEC-NP) and parkinsonism (IEC-PKS), in patients with relapsed/refractory multiple myeloma (RRMM) treated with ciltacabtagene autoleucel (cilta-cel) in standard-of-care practice (SOC). Among 235 RRMM patients who received cilta-cel, 15 (6.4%) developed IEC-NP and 9 (3.8%) developed IEC-PKS with one patient developing both. Pre-infusion, patients with age >75 years, bone marrow plasma cells ≥20%, or involved free light chain ≥20 mg/dL had increased odds of IEC-PKS. Post-infusion, patients who developed ICANS, received higher cumulative steroid doses or received >1 dose of tocilizumab also had increased odds of IEC-PKS. High peak absolute lymphocyte count (ALCpeak) was a statistically significant predictor on univariate and multivariate analysis for IEC-NP and IEC-PKS. ALC_peak ≥ 3 × 10⁹/L was identified as a meaningful threshold (AUC = 0.838) to predict for late onset neurotoxicity. An ALC_peak ≥ 3 × 10⁹/L conferred a positive predictive value for delayed neurotoxicity of 31% vs a negative predictive value of 98% in patients with ALC_peak < 3 × 10⁹/L. All IEC-NP patients received steroid +/- IVIG; 87% had complete resolution of their cranial neuropathies (median 57 days). Four patients with IEC-PKS received cyclophosphamide (1.5-2 g/m²) within 1-13 days of symptom onset and all had observable symptom improvement within 1-2 days.