免疫检查点抑制剂 (ICI) 疗法极大地改变了多种癌症的临床格局，并且 ICI 的使用持续扩大到多种癌症类型。低基线清除率 (CL) 和/或治疗期间 CL 大幅降低与更好的临床反应和更长的生存期相关。其他单克隆抗体 (mAb) 在癌症和其他疾病中也出现了类似的现象，突显了 mAb 临床药理学的一个特征，该特征可能在各种 mAb 和疾病之间共享。尽管人们很容易将不良结果归因于药物暴露量低以及由于高 CL 导致的靶点参与度低，但大多数 ICI 相对平坦的暴露-反应关系并不支持这种推测，因为大多数 ICI 的暴露-反应关系较高，较高的剂量或暴露不太可能提供额外的益处。相反，升高和/或增加的 CL 可能是固有耐药表型的替代标志，而这种表型不能通过最大化药物暴露来逆转。连接 ICI 清除、治疗效果和耐药性的机制尚不清楚，并且可能是多因素的。因此，为了探索 ICI CL 作为早期疗效标志物的潜力，本综述强调了所有 FDA 批准的 ICI 的 CL 特征和 CL 反应关系的异同，并且我们将它们与选定的非 ICI mAb 进行了比较和对比。我们还讨论了可能将 mAb CL 与疗效联系起来的潜在机制，并强调了现有的知识差距和未来方向，其中需要进行更多的临床和临床前研究，以清楚地了解基线和/或时变 CL 在预测基于 ICI 的治疗反应中的价值。

Immune checkpoint inhibitor (ICI) therapy has dramatically changed the clinical landscape for several cancers, and ICI use continues to expand across many cancer types. Low baseline clearance (CL) and/or a large reduction of CL during treatment correlates with better clinical response and longer survival. Similar phenomena have also been reported with other monoclonal antibodies (mAbs) in cancer and other diseases, highlighting a characteristic of mAb clinical pharmacology that is potentially shared among various mAbs and diseases. Though tempting to attribute poor outcomes to low drug exposure and arguably low target engagement due to high CL, such speculation is not supported by the relatively flat exposure-response relationship of most ICIs where a higher dose or exposure is not likely to provide additional benefit. Instead, an elevated and/or increasing CL could be a surrogate marker of the inherent resistant phenotype that cannot be reversed by maximizing drug exposure. The mechanisms connecting ICI clearance, therapeutic efficacy, and resistance are unclear and likely to be multifactorial. Therefore, to explore the potential of ICI CL as an early marker for efficacy, this review highlights the similarities and differences of CL characteristics and CL-response relationships for all FDA-approved ICIs, and we compare and contrast these to selected non-ICI mAbs. We also discuss underlying mechanisms that potentially link mAb CL with efficacy and highlight existing knowledge gaps and future directions where more clinical and preclinical investigations are warranted to clearly understand the value of baseline and/or time-varying CL in predicting response to ICI-based therapeutics.