多发性骨髓瘤中 ciltacabtagene autoleucel CAR-T 治疗后免疫效应细胞相关迟发性神经毒性的临床病程、危险因素和缓解策略

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 10 9 /L was identified as a meaningful threshold (AUC = 0. 838) to predict for late onset neurotoxicity. An ALC peak 3 10 9 /L conferred a positive predictive value for delayed neurotoxicity of 31% vs a negative predictive value of 98% in patients with ALC peak < 3 10 9 /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/m 2 ) within 1-13 days of symptom onset and all had observable symptom improvement within 1-2 days.