Department of Medical Oncology, Johns Hopkins University, Baltimore, MD, USA.
Johns Hopkins Kimmel Cancer Center, Baltimore, MD, USA.
Ann Hematol. 2022 Jan;101(1):1-10. doi: 10.1007/s00277-021-04690-x. Epub 2021 Dec 28.
Immune checkpoint blockade has demonstrated durable clinical benefits in a variety of malignancies. These immune checkpoint inhibitors (ICIs) produce unwanted autoimmune reactions due to an impaired self-tolerance. Hematologic immune-related adverse events (heme-irAEs) have been increasingly reported in the literature with a reported fatality rate of 12%. In this review, we illustrate 3 cases treated at Johns Hopkins Hospital for ICI-induced agranulocytosis, aplastic anemia, and thrombocytopenia. We then summarize the available evidence regarding the incidence and prevalence of heme-irAEs. We identified immune thrombocytopenia and hemolytic anemia as the most commonly reported heme-irAEs which are more commonly observed with nivolumab therapy. Median time to onset of heme-irAEs varies between patients but occurs earlier with CTLA-4 inhibitors than with anti-PD-L1/PD-1 agents. We also describe the current challenges regarding the recurrence of heme-irAEs despite immune checkpoint blockade termination. We provide the available evidence supporting a mixed T-cell and B-cell immune-mediated response. Finally, we review the treatment algorithm of these complications and provide treatment alternatives to steroid-refractory cases.
免疫检查点阻断在多种恶性肿瘤中显示出持久的临床获益。这些免疫检查点抑制剂（ICI）由于自身耐受性受损而产生不必要的自身免疫反应。血液学免疫相关不良事件（heme-irAEs）在文献中越来越多地被报道，其死亡率为 12%。在这篇综述中，我们展示了在约翰霍普金斯医院治疗的 3 例因 ICI 引起的粒细胞缺乏症、再生障碍性贫血和血小板减少症的病例。然后，我们总结了关于血液学免疫相关不良事件的发生率和患病率的现有证据。我们确定免疫性血小板减少症和溶血性贫血是最常见的血液学免疫相关不良事件，在纳武单抗治疗中更常见。血液学免疫相关不良事件的发病中位时间因患者而异，但 CTLA-4 抑制剂比抗 PD-L1/PD-1 药物更早发生。我们还描述了尽管免疫检查点阻断终止但血液学免疫相关不良事件复发的当前挑战。我们提供了支持混合 T 细胞和 B 细胞免疫介导反应的现有证据。最后，我们回顾了这些并发症的治疗算法，并为类固醇难治性病例提供了替代治疗方案。
