Isaacs Dayna Jill, Kathuria-Prakash Nikhita, Hilder Robin, Lechner Melissa G, Drakaki Alexandra
Department of Medicine, UCLA David Geffen School of Medicine, Los Angeles, CA 90095, USA.
Division of Hematology and Oncology, Department of Medicine, UCLA David Geffen School of Medicine, Los Angeles, CA 90095, USA.
Curr Cancer Rep. 2024 Feb 20;5(1):168-180. doi: 10.25082/ccr.2023.01.004. Epub 2024 Jan 29.
To evaluate the frequency and severity of irAEs in patients with pre-existing autoimmunity, including irAE-related morbidity and mortality, irAE-related management and resolution, and outcome of ICI rechallenge, to better understand the treatment options for this vulnerable patient population.
We designed a retrospective, single-center, case-control study at a large, academic medical center to evaluate the incidence and severity of irAEs in patients with pre-existing autoimmunity compared to controls. Controls were matched 2:1 for age, sex, cancer histology, and ICI class. Patients were identified with ICD 9 and 10 codes followed by manual chart extraction. Cases were defined as patients with pre-existing, systemic autoimmunity. The primary outcome was severe irAE (Grade 3 or higher by Common Terminology Criteria for Adverse Events) within 6 months of ICI therapy. Secondary outcomes included response to ICIs, resolution of the irAE, ICI rechallenge success, and survival. Statistical analyses were performed by Chi-square, Fishers exact, Mann-Whitney, and Log-rank tests.
Of 3,130 patients treated with ICIs from 2015-2021, 28 cases with pre-existing autoimmune disease were identified and were matched with 56 controls. Pre-existing autoimmune conditions included antiphospholipid syndrome, inflammatory polyarthritis, juvenile rheumatoid arthritis, multiple sclerosis, psoriatic arthritis, rheumatoid arthritis, and type I diabetes. Multiple cancer histologies, including genitourinary, gynecologic, head & neck, hepatobiliary, lung, melanoma, and pancreatic, were represented. Six of 28 cases (21.4%) experienced severe irAEs compared to 9/56 (16.1%) controls; the odds of developing a severe irAE were not significantly different (OR 0.43, 95% CI 0.083-2.33, = 0.627, ns). Moreover, there were no significant differences in overall survival or tumor response between the two groups. The majority of irAEs resolved without long-term sequelae (66.7% of cases, 55.6% of controls). The majority of patients who were rechallenged with ICIs were successful in continuing therapy (66.7% of cases, 100% of controls).
Our study suggests that patients with pre-existing autoimmune disease can be treated with ICI cancer therapies and experience rates of severe irAEs and overall survival that are similar to those of the general population. These data can aid oncologists in discussing risks and benefits of ICIs when treating patients with pre-existing autoimmunity and solid tumors.
评估已有自身免疫性疾病的患者中免疫相关不良反应（irAEs）的发生频率和严重程度，包括与irAE相关的发病率和死亡率、irAE相关的管理和缓解情况，以及免疫检查点抑制剂（ICI）再次治疗的结果，以更好地了解针对这一脆弱患者群体的治疗选择。
我们在一家大型学术医疗中心设计了一项回顾性、单中心、病例对照研究，以评估已有自身免疫性疾病的患者与对照组相比irAEs的发生率和严重程度。对照组按年龄、性别、癌症组织学和ICI类别以2:1进行匹配。通过国际疾病分类第9版和第10版编码识别患者，随后进行手动病历提取。病例定义为已有全身性自身免疫性疾病的患者。主要结局是ICI治疗6个月内发生的严重irAE（根据不良事件通用术语标准为3级或更高）。次要结局包括对ICI的反应、irAE的缓解、ICI再次治疗的成功情况和生存率。采用卡方检验、Fisher精确检验、Mann-Whitney检验和对数秩检验进行统计分析。
在2015年至2021年接受ICI治疗的3130例患者中，识别出28例已有自身免疫性疾病的病例，并与56例对照组进行匹配。已有自身免疫性疾病包括抗磷脂综合征、炎性多关节炎、青少年类风湿关节炎、多发性硬化症、银屑病关节炎、类风湿关节炎和1型糖尿病。涵盖了多种癌症组织学类型，包括泌尿生殖系统、妇科、头颈部、肝胆、肺、黑色素瘤和胰腺。28例病例中有6例（21.4%）发生严重irAE，而对照组为9/56（16.1%）；发生严重irAE的几率无显著差异（比值比0.43，95%置信区间0.083 - 2.33，P = 0.627，无统计学意义）。此外，两组之间的总生存率或肿瘤反应无显著差异。大多数irAE得到缓解，无长期后遗症（病例组为66.7%，对照组为55.6%）。大多数接受ICI再次治疗的患者成功继续治疗（病例组为66.7%，对照组为100%）。
我们的研究表明，已有自身免疫性疾病的患者可以接受ICI癌症治疗，其严重irAE发生率和总生存率与普通人群相似。这些数据有助于肿瘤学家在治疗已有自身免疫性疾病和实体瘤的患者时讨论ICI的风险和益处。
