From the Department of Neurology (C.M.Q., P.R., S.E.C., S.B.), Brigham and Women's Hospital, Boston, MA; Department of Neurology (A.J.G., J.C.P.), Johns Hopkins University School of Medicine, Baltimore, MD; Department of Neurology (H.K., T.E.B., I.K.), NYU Grossman School of Medicine, New York; Department of Neurology (A.B.W., E.A.), University of Colorado School of Medicine, Aurora; Department of Neurology (C.S.d.C., V.B.), Rutgers-Robert Wood Johnson Medical School, New Brunswick, NJ; Department of Neurology (J.L., P.C.), Stony Brook University Medical Center, NY; Sidney Kimmel Comprehensive Cancer Center (J.C.M.), Johns Hopkins University School of Medicine, Baltimore, MD; Department of Neurology (K.M.G.), Stanford University, CA; Medical Partnership 4 MS+ (MP4MS+) (D.K.), LaBelle, FL.
Neurology. 2024 Dec 10;103(11):e210003. doi: 10.1212/WNL.0000000000210003. Epub 2024 Nov 14.
Immune checkpoint inhibitors (ICIs) are increasingly used against various cancers but are associated with immune-related adverse events (irAEs). Risk of irAEs may be higher in patients with certain preexisting autoimmune diseases, and these patients may also experience exacerbation of the underlying autoimmune disease following ICI initiation. People with multiple sclerosis (MS) have mostly been excluded from clinical trials of ICIs, so data on the safety of ICIs in MS are limited. This study aims to assess the rate of MS activity, as well as neurologic and nonneurologic irAEs in persons with MS treated with ICIs for cancer.
Participating sites were invited to this retrospective observational study through the Medical Partnership 4 MS+ listserv. Seven large academic centers participated in the study, each conducting a systematic search of their electronic medical record system for patients with MS and history of ICI treatment. The participating neurologist reviewed each chart individually to ensure the inclusion criteria were met. Demographics and data on MS and cancer history, treatments, and outcomes were abstracted from patient charts using a structured instrument.
We identified 66 people with MS (median age 66 years, 73% female, 68% not on disease-modifying therapy for MS) who were treated with ICIs for lung cancer (35%), melanoma (21%), or another oncologic indication. During post-ICI follow-up (median: 11.7 months, range 0.2-106.3 months), 2 patients (3%) had relapse or MRI activity, 3 (5%) had neurologic irAEs, and 21 (32%) had nonneurologic irAEs. At the last follow-up, 25 (38%) participants had partial or complete remission of their cancer, while 35 (53%) were deceased.
In this multi-institutional systematic retrospective study of predominantly older patients with MS, most of whom were not on disease-modifying therapy, MS activity and neurologic irAEs following ICI treatment were rare. These data suggest that preexisting MS should not preclude the use of ICIs for cancer in older patients, but the results may not be generalizable to younger patients with active MS. Prospective studies of ICI safety that enroll younger patients with MS are needed.
免疫检查点抑制剂（ICIs）在多种癌症的治疗中得到了越来越多的应用，但与免疫相关的不良反应（irAEs）有关。某些自身免疫性疾病患者发生 irAEs 的风险可能更高，并且这些患者在开始使用 ICI 后可能会出现基础自身免疫性疾病的恶化。多发性硬化症（MS）患者大多被排除在 ICI 的临床试验之外，因此关于 MS 患者使用 ICI 的安全性数据有限。本研究旨在评估接受 ICI 治疗癌症的 MS 患者的 MS 活动、神经系统和非神经系统 irAEs 的发生率。
通过 Medical Partnership 4 MS+列表服务器邀请参与的站点参加这项回顾性观察研究。7 个大型学术中心参与了这项研究，每个中心都对其电子病历系统进行了系统性搜索，以寻找患有 MS 且有 ICI 治疗史的患者。参与的神经科医生单独审查了每个病历以确保符合纳入标准。使用结构化工具从患者病历中提取人口统计学数据以及 MS 和癌症病史、治疗和结局的数据。
我们共确定了 66 名 MS 患者（中位年龄 66 岁，73%为女性，68%未接受 MS 的疾病修正治疗），他们因肺癌（35%）、黑色素瘤（21%）或其他肿瘤指征接受了 ICI 治疗。在接受 ICI 治疗后的随访期间（中位数：11.7 个月，范围 0.2-106.3 个月），2 名患者（3%）出现了复发或 MRI 活动，3 名患者（5%）出现了神经系统 irAEs，21 名患者（32%）出现了非神经系统 irAEs。在最后一次随访时，25 名患者（38%）的癌症部分或完全缓解，而 35 名患者（53%）死亡。
在这项多机构的系统回顾性研究中，我们纳入了患有 MS 的患者，这些患者主要为年龄较大、大多数未接受疾病修正治疗的患者，在接受 ICI 治疗后，MS 活动和神经系统 irAEs 较为罕见。这些数据表明，对于老年患者而言，先前存在的 MS 不应排除使用 ICI 治疗癌症，但结果可能不适用于患有活动性 MS 的年轻患者。需要开展前瞻性研究，以评估年轻 MS 患者使用 ICI 的安全性。
