Cicala Giuseppe, Russo Giulia, Santoro Vincenza, Franchina Tindara, Silvestris Nicola, Santarpia Mariacarmela, Spina Edoardo, Barbieri Maria Antonietta
Department of Clinical and Experimental Medicine, University of Messina, 98125 Messina, Italy.
Department of Biomedical and Dental Sciences and Morpho-Functional Imaging, University of Messina, 98125 Messina, Italy.
Pharmaceuticals (Basel). 2024 Sep 25;17(10):1266. doi: 10.3390/ph17101266.
: Monoclonal antibodies (mAbs) have revolutionized multiple myeloma (MM) treatment. However, post-marketing data on their neuropsychiatric safety are limited. This study aimed to evaluate neuropsychiatric adverse events (AEs) related to mAbs used for MM through a retrospective pharmacovigilance analysis using the Food and Drug Administration (FDA) Adverse Events Reporting System (FAERS) database. : Individual case safety reports (ICSRs) from 2015 to 2023 with at least one neuropsychiatric AE and one of the MM-approved mAbs as the suspected drug (i.e., daratumumab, elotuzumab, isatuximab, belantamab mafodotin, teclistamab, elranatamab, and talquentamab) were analyzed using descriptive and disproportionality approaches. : Unknown signals of disproportionate reporting (SDR) included the following: cerebral infarction for daratumumab ( = 45; reporting odds ratio (ROR) = 2.39, 95% confidence interval (CI) = 1.79-3.21; information component (IC) = 1.54, IC-IC = 1.05-1.9), elotuzumab (25; 7.61, 5.13-11.28; 3.03, 2.37-3.51), and isatuximab (10; 2.56, 1.38-4.76; 1.67, 0.59-2.4); mental status changes for daratumumab (40; 2.66, 1.95-3.63; 1.67, 1.14-2.04) and belantamab mafodotin (10; 4.23, 2.28-7.88; 2.3, 1.22-3.03); an altered state of consciousness for daratumumab (32; 1.97, 1.39-2.78; 1.32, 0.73-1.74) and belantamab mafodotin (6; 2.35, 1.05-5.23; 1.6, 0.19-2.52); Guillain-Barre syndrome (GBS) for daratumumab (23; 6.42, 4.26-9.69; 2.81, 2.11-3.3), isatuximab (8; 10.72, 5.35-21.48; 3.57, 2.35-4.37), and elotuzumab (3; 4.74, 1.53-14.7; 2.59, 0.52-3.8); and orthostatic intolerance for daratumumab (10; 12.54, 6.71-23.43; 3.75, 2.67-4.48) and elotuzumab (4; 28.31, 10.58-75.73; 5, 3.24-6.08). : Our analysis highlighted several previously unacknowledged SDRs for MM-approved mAbs. Given the complex and not entirely understood etiology of some neuropsychiatric AEs, including GBS, further investigations are necessary.
单克隆抗体（mAbs）彻底改变了多发性骨髓瘤（MM）的治疗方式。然而，关于其神经精神安全性的上市后数据有限。本研究旨在通过使用美国食品药品监督管理局（FDA）不良事件报告系统（FAERS）数据库进行回顾性药物警戒分析，评估与用于MM的mAbs相关的神经精神不良事件（AEs）。
对2015年至2023年期间的个体病例安全报告（ICSRs）进行分析，这些报告至少有一项神经精神AE，且将MM批准的mAbs之一作为可疑药物（即达雷妥尤单抗、埃罗妥珠单抗、isatuximab、贝兰他单抗莫福汀、替西妥单抗、埃拉纳妥单抗和talquentamab），采用描述性和不成比例性方法进行分析。
不成比例报告（SDR）的未知信号包括：达雷妥尤单抗导致的脑梗死（ = 45；报告比值比（ROR） = 2.39，95%置信区间（CI） = 1.79 - 3.21；信息成分（IC） = 1.54，IC - IC = 1.05 - 1.9）、埃罗妥珠单抗（25；7.61，5.13 - 11.28；3.03，2.37 - 3.51）和isatuximab（10；2.56，1.38 - 4.76；1.67，0.59 - 2.4）；达雷妥尤单抗导致的精神状态改变（40；2.66，1.95 - 3.63；1.67，1.14 - 2.04）和贝兰他单抗莫福汀（10；4.23，2.28 - 7.88；2.3，1.22 - 3.03）；达雷妥尤单抗导致的意识状态改变（32；1.97，1.39 - 2.78；1.32，0.73 - 1.74）和贝兰他单抗莫福汀（6；2.35，1.05 - 5.23；1.6，0.19 - 2.52）；达雷妥尤单抗导致的吉兰 - 巴雷综合征（GBS）（23；6.42，4.26 - 9.69；2.81，2.11 - 3.3）、isatuximab（8；10.72，5.35 - 21.48；3.57，2.35 - 4.37）和埃罗妥珠单抗（3；4.74，1.53 - 14.7；2.59，0.52 - 3.8）；达雷妥尤单抗导致的体位性不耐受（10；12.54，6.71 - 23.43；3.75，2.67 - 4.48）和埃罗妥珠单抗（4；28.31，10.58 - 75.73；5，3.24 - 6.08）。
我们的分析突出了几种MM批准的mAbs以前未被认识到的SDR。鉴于包括GBS在内的一些神经精神AE的病因复杂且尚未完全理解，进一步的研究是必要的。
