Cancers:免疫检查点抑制剂治疗期间免疫相关内分泌不良事件的临床表现

2022-07-07 从医路漫漫 MedSci原创

虽然与其他全身性抗癌药物相比,ICIs具有独特的毒性,但它们导致了一系列新的不良事件,称为免疫相关不良事件(irAE),有时可能是致命的。

背景:免疫检查点抑制剂(ICIs)的开发彻底改变了癌症治疗,显著改善了各种恶性肿瘤的临床结果。虽然与其他全身性抗癌药物相比,ICIs具有独特的毒性,但它们导致了一系列新的不良事件,称为免疫相关不良事件(irAE),有时可能是致命的。irAEs被定义为具有潜在免疫学基础的ICI治疗开始后出现的副作用。这些irAEs可以影响任何器官,尽管最常见的是皮肤、胃肠道、内分泌器官和肺受到影响。我们中心最近的一项研究发现,内分泌疾病是最常见的irae(8.1%)。在一项荟萃分析和系统综述中,内分泌irAE的发生率据报告为甲状腺功能减退6.6%,甲状腺功能亢进2.9%,垂体炎1.3%,胰岛素依赖型糖尿病0.2%(IDDM)。内分泌疾病中持续激素功能障碍(包括甲状腺和垂体功能障碍以及IDDM)的确切时间表和预测因素尚未完全确定。这些特征对ICIs患者和随后发生内分泌irAE的患者的内分泌irAE筛查和随访频率有直接影响。最近的研究表明,irAE的存在与生存结果相关,与未出现irAE的患者相比,出现irAE的患者预后更好,并且在内分泌irAE中观察到相同的相关性,本研究还试图通过评估内分泌irAE对生存结果的影响来验证这些发现。

目的:我们分析了内分泌异常的临床过程,包括甲状腺和垂体功能障碍以及胰岛素依赖型糖尿病(IDDM),确定了与持续性甲状腺功能障碍相关的因素,并确定了内分泌异常与生存参数之间的关系。

方法:这项回顾性观察研究招募了2015年6月至2020年12月期间在新加坡国立大学癌症研究所接受抗PD-1、抗PD-L1和/或抗CTLA-4治疗并出现内分泌irAE的转移性癌症患者。

结果:评估了66例内分泌irAE患者,中位随访时间为15.7个月。甲状腺功能障碍、垂体功能障碍和IDDM的中位发病时间分别为1.8个月(范围:0.3-15.8个月)、6.8个月(范围:1.5-27.3个月)和7.8个月(范围:1.4-9.1个月)。甲状腺功能障碍时甲状腺过氧化物酶抗体(TPOAb)和/或甲状腺球蛋白抗体(TgAb)阳性与持续性甲状腺功能障碍相关(OR 11.6,95% CI 1.3–570.8,p = 0.02或8.8,95%可信区间分别为1.3-106.9,p = 0.01)。所有垂体irAE患者都有中枢性低皮质醇症。所有IDDM患者都有4级irAE。内分泌irAE患者的中位生存期较长。

图1 各个irAE的时变发生率。

表1 甲状腺功能障碍患者的特征(n = 49)。

图2 根据甲状腺irAE状态绘制的总生存率Kaplan-Meier曲线。

表2免疫治疗后出现垂体功能障碍的患者(n = 18)。

图3 根据垂体irAE状态绘制的总生存率Kaplan-Meier曲线。

图4 根据内分泌irAE状态绘制的总生存率Kaplan-Meier曲线。

结论:内分泌疾病与非进展性疾病相关。应根据每种内分泌疾病的临床过程来选择内分泌干扰物的筛查和随访方法。鉴于其广泛的中位发病时间,早期筛查是必须的。

原文出处:Chieng JHL,  Htet ZW,  Zhao JJ,Clinical Presentation of Immune-Related Endocrine Adverse Events during Immune Checkpoint Inhibitor Treatment.Cancers (Basel) 2022 May 29;14(11) 

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    2022-10-16 anminleiryan
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    2022-07-27 jklm09
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    2022-07-27 gwc392
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