Division of Hematology and Oncology, University of Louisville, Louisville, KY, USA.
Division of Hematology and Oncology, University of Louisville, Louisville, KY, USA.
Curr Probl Cancer. 2022 Aug;46(4):100864. doi: 10.1016/j.currproblcancer.2022.100864. Epub 2022 May 2.
In recent years, immune checkpoint inhibitors (ICIs) have been approved for a growing number of cancer types. Approximately a quarter of cancer patients have a concomitant diagnosis of autoimmune disorders (AID). Activation of the immune system with ICIs poses a potential risk of AID worsening, thus, the majority of the ICI clinical trials excluded these patients from the study. There is a paucity of data regarding the benefits and risks of ICIs in cancer patients with AIDs. The primary objectives of this study were to determine the incidence of immunotherapy-related AID worsening and all immunotherapy-related adverse events (irAEs). Secondary outcomes were time to AID worsening and survival difference. All adult patients (age >=18 years) with solid malignancy who received ICIs between Jan 2016 and June 2019 were identified using the University of Louisville pharmacy database. Medical records were reviewed to include all the patients with preexisting AIDs. Descriptive statistics were used to determine the incidence of AID worsening and all irAEs. Baseline characteristics were compared between cancer patients with vs without AID worsening using Pearson chi2 and Student's t-test, where appropriate. Multivariate Cox regression analysis was used to compare survival between the 2 groups. A total of 40 patients with AIDs were identified during the study period. The cancer types were melanoma (57.5%), lung (15%), breast (5%), and others (22.5%). AIDs were rheumatological (52.5%), dermatologic (20%), gastroenterological (12.5%), neurologic (12.5%), and hematological (2.5%). The incidence of all irAEs was 60% (grade >=3 in 20%) and AID worsening was 40% (grade >=3 in 15%). The median time from ICI initiation to AID worsening was 94.5 (range 21-431) days. In multivariate Cox regression analysis, adjusted for demographics, cancer type, and stage, survival was similar for patients who had AID worsening vs those who did not (HR 0.30 (95%CI 0.06-1.40, P = 0.128). In our single-institution study, cancer patients with preexisting AID do have an increased risk of irAEs with high-grade toxicities in 20% compared to historically reported 5% in the general cancer population. About 15% of patients reported grade >=3 worsening of their AIDs. Although the risk of irAEs is numerically higher in patients with AIDs, it may be acceptable to the patients if the potential benefits of ICIs outweigh the risks.
近年来，免疫检查点抑制剂（ICIs）已被批准用于越来越多的癌症类型。大约四分之一的癌症患者同时患有自身免疫性疾病（AID）。ICI 激活免疫系统可能会导致 AID 恶化，因此，大多数 ICI 临床试验将这些患者排除在研究之外。关于患有 AID 的癌症患者使用 ICI 的益处和风险的数据很少。本研究的主要目的是确定免疫治疗相关 AID 恶化和所有免疫治疗相关不良事件（irAE）的发生率。次要结果是 AID 恶化和生存差异的时间。使用路易斯维尔大学药房数据库确定了 2016 年 1 月至 2019 年 6 月期间接受 ICI 治疗的所有成年实体恶性肿瘤患者。回顾病历以纳入所有患有预先存在的 AID 的患者。使用描述性统计数据确定 AID 恶化和所有 irAE 的发生率。使用 Pearson chi2 和学生 t 检验（如适用）比较癌症患者有无 AID 恶化的基线特征。使用多变量 Cox 回归分析比较两组的生存情况。在研究期间共发现 40 例患有 AID 的患者。癌症类型为黑色素瘤（57.5%）、肺癌（15%）、乳腺癌（5%）和其他（22.5%）。AID 为风湿性疾病（52.5%）、皮肤病学（20%）、胃肠病学（12.5%）、神经病学（12.5%）和血液学（2.5%）。所有 irAE 的发生率为 60%（≥3 级占 20%），AID 恶化率为 40%（≥3 级占 15%）。从 ICI 开始到 AID 恶化的中位时间为 94.5 天（范围 21-431 天）。在多变量 Cox 回归分析中，根据人口统计学、癌症类型和分期进行调整后，AID 恶化患者的生存率与未恶化患者相似（HR 0.30（95%CI 0.06-1.40，P=0.128）。在我们的单机构研究中，与一般癌症人群中报告的 5%相比，患有预先存在的 AID 的癌症患者发生 irAE 的风险更高，且毒性更高（≥3 级占 20%）。约 15%的患者报告其 AID 恶化程度≥3 级。尽管 AID 患者的 irAE 风险在数值上较高，但如果 ICI 的潜在益处超过风险，对患者来说可能是可以接受的。
