Fletcher Kylie, Machaalani Marc, El Hajj Chehade Razane, Nassar Amin H, Nawfal Rashad, Manos Michael, Menzies Alexander M, Aboubakar-Nana Frank, Hassel Jessica C, Pinato David J, Johnson Alexandra, Olsson-Brown Anna C, Carlino Matteo S, Malgeri Andrea, Cortellini Alessio, Singh Aditi, Parikh Kaushal, Kim So Yeon, Naqash Abdul Rafeh, Long Georgina V, Challa Pavan, Choueiri Toni K, Sharon Elad, Shah Shailee, Johnson Douglas B
Vanderbilt University School of Medicine, Nashville, Tennessee.
Dana Farber Cancer Institute, Boston, Massachusetts.
JAMA Netw Open. 2025 Jun 2;8(6):e2513727. doi: 10.1001/jamanetworkopen.2025.13727.
Immune checkpoint inhibitors (ICIs) are efficacious in many cancer types but can produce immune-related adverse events (irAEs). As such, patients with preexisting autoimmune disorders are often excluded from clinical trials, although subsequent studies have shown that many of these patients have acceptable ICI tolerance. The safety and efficacy of ICIs among patients with preexisting neurologic autoimmune disorders (NAIDs) is not well characterized.
To evaluate the safety and clinical outcomes associated with ICI therapy among patients with NAIDs.
DESIGN, SETTING, AND PARTICIPANTS: This multicenter retrospective cohort study included patients with cancer who were treated with ICIs between October 2013 and May 2023 and had preexisting multiple sclerosis (MS), myasthenia gravis (MG), Guillain-Barré syndrome (GBS), and other NAIDs as well as a control cohort of patients with Parkinson disease (PD).
ICI therapy.
Demographic and clinical characteristics (neurologic disability, active or recent immunosuppression), ICI outcomes (response, progression-free survival [PFS], and overall survival [OS]), and safety outcomes (NAID exacerbation, irAEs) were collected.
A total of 135 patients were included; the median (range) age was 72 (40-88) years, 84 (62%) were men, and 51 (38%) were women. A total of 45 patients had MS; 18, MG; 10, GBS; 5, another NAID; and 57, PD. Exacerbations occurred most frequently in MG (12 of 18 patients [67%]), often resulting in hospitalization (6 [50%]) or death (2 [17%]), with much lower rates in the MS cohort (8 of 45 patients [18%]). Ten patients with a history of GBS tolerated ICI without exacerbations, although 1 developed a fatal case of Lambert Eaton myasthenic syndrome following ICI treatment. No differences in response rate, PFS, or OS were observed between NAID groups.
In this cohort study of ICI use in NAIDs, patients with MG had frequent and more severe exacerbations, while those with MS had few exacerbations. No obvious differences in survival between groups were observed. ICI may be an option for many patients with appropriate oncologic indications and preexisting NAIDs.
免疫检查点抑制剂（ICI）在多种癌症类型中有效，但可产生免疫相关不良事件（irAE）。因此，患有自身免疫性疾病的患者通常被排除在临床试验之外，尽管后续研究表明这些患者中的许多人对ICI具有可接受的耐受性。ICI在患有神经系统自身免疫性疾病（NAID）的患者中的安全性和有效性尚未得到充分描述。
评估NAID患者接受ICI治疗的安全性和临床结局。
设计、设置和参与者：这项多中心回顾性队列研究纳入了2013年10月至2023年5月期间接受ICI治疗且患有多发性硬化症（MS）、重症肌无力（MG）、吉兰-巴雷综合征（GBS）和其他NAID的癌症患者以及帕金森病（PD）患者的对照队列。
ICI治疗。
收集人口统计学和临床特征（神经功能障碍、活动性或近期免疫抑制）、ICI结局（缓解、无进展生存期[PFS]和总生存期[OS]）以及安全性结局（NAID加重、irAE）。
共纳入135例患者；中位（范围）年龄为72（40 - 88）岁，84例（62%）为男性，51例（38%）为女性。共有45例患者患有MS；18例患有MG；10例患有GBS；5例患有其他NAID；57例患有PD。MG患者中加重情况最常见（18例患者中有12例[67%]），常导致住院（6例[50%]）或死亡（2例[17%]），MS队列中的发生率则低得多（45例患者中有8例[18%]）。10例有GBS病史的患者耐受ICI且未加重，尽管1例在ICI治疗后发生了致命的兰伯特-伊顿肌无力综合征。NAID组之间在缓解率、PFS或OS方面未观察到差异。
在这项关于NAID患者使用ICI的队列研究中，MG患者加重频繁且更严重，而MS患者加重较少。各亚组间生存率无明显差异。对于许多有适当肿瘤学指征且患有NAID的患者，ICI可能是一种选择。
