Reply: Immunosuppression Does Not Reduce Antitumor Efficacy.
Reply: Immunosuppression Does Not Reduce Antitumor Efficacy.
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答复：免疫抑制不会降低抗肿瘤功效。
DOI：
10.1016/j.jacc.2018.06.005
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发表时间：
2018
影响因子：
24
通讯作者：
Neilan,TomasG
中科院分区：
文献类型：
--
作者：
Mahmood,SyedS;Sullivan,RyanJ;Reynolds,KerryL;Neilan,TomasG
我们感谢曹博士对我们的论文(1)的评论，并提出了一个关键问题：使用全身免疫抑制是否会降低免疫检查点抑制剂的抗肿瘤功效？目前还没有关于免疫检查点抑制剂对心肌炎的免疫抑制是否会降低这些药物的抗肿瘤疗效的数据，但当所有免疫相关不良事件（irAEs）合并时，有重要的数据。例如，在一项对近300名接受免疫检查点抑制剂（ipilimumab，一种抗ctla4抗体）治疗的转移性黑色素瘤患者的研究中，85%的患者发生了irAE；其中，35%接受皮质类固醇治疗，其中三分之一接受类固醇治疗的患者需要进一步接受英夫利昔单抗治疗(2)。接受免疫抑制的患者总体中位生存期和2年生存期与未接受免疫抑制的患者相似。使用免疫抑制疗法来管理irae似乎也不会影响癌症对抗程序性细胞死亡受体1抗体检查点抑制的反应(3)。在对576例黑色素瘤患者的汇总分析中，Weber等人报道24%的患者需要免疫抑制来进行irAE治疗，并且接受免疫抑制治疗的患者和未接受免疫抑制治疗的患者在客观缓解率上没有差异（29.8%对31.8%）。另一个问题是使用的免疫抑制剂量是否会影响免疫检查点抑制剂的抗肿瘤反应。在我们的研究(1)中，我们发现用于治疗心肌炎的高剂量类固醇与较低的心脏不良事件发生率相关。具体来说，我们发现那些接受等效剂量为2.06 mg/kg甲基强的松龙治疗的患者比接受0.8 mg/kg甲基强的松龙治疗的患者有更低的主要心脏不良事件发生率。在Horvat等人(2)的研究中，类固醇的平均剂量（以sol - medrol当量计算）为0.8 mg/kg，没有数据表明在该队列中，更高剂量的类固醇是否会影响肿瘤反应。
We thank Dr. Cao for his comments on our paper (1) and for asking a critical question: Does the use of systemic immunosuppression reduce the antitumor efficacy of immune checkpoint inhibitors? There are no data on whether immunosuppression for myocarditis from immune checkpoint inhibitors reduces the antitumor efficacy of these agents, but there are significant data when all immune-related adverse events (irAEs) are combined. For example, in a study of almost 300 patients with metastatic melanoma treated with an immune checkpoint inhibitor (ipilimumab, an anti-CTLA4 antibody), 85% developed an irAE; of these, 35% were treated with corticosteroids, with one third of these steroid recipients requiring further therapy with infliximab (2). Patients receiving immunosuppression had an overall median and 2-year survival similar to those who did not receive immunosuppression.The use of immunosuppressive therapy to manage irAEs also does not seem to affect the cancer response to checkpoint inhibition with anti-programmed cell death receptor 1 antibodies (3). In a pooled analysis of 576 patients with melanoma, Weber et al. reported that 24% required immunosuppression for an irAE, and there was no difference in the objective response rate between those who received immunosuppressive treatment and those who did not (29.8% vs. 31.8%). An additional question is whether the dose of immunosuppression used may affect the antitumor response of immune checkpoint inhibitors. In our study (1), we found that higher doses of steroids for the treatment of myocarditis was associated with a lower rate of adverse cardiac events. Specifically, we found that those treated with a methylprednisolone-equivalent dose of 2.06 mg/kg had a lower rate of major adverse cardiac events than those treated with 0.8 mg/kg. In the study by Horvat et al.(2), the average steroid dose (in Solu-Medrol-equivalent) was 0.8 mg/kg, and there are no data on whether higher doses of steroids affected tumor response in that cohort.
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作者：
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DOI：
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期刊：
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影响因子：
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