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A closer look at immune-mediated myocarditis in the era of combined checkpoint blockade and targeted therapies.

在联合检查点阻断和靶向治疗的时代仔细观察免疫介导的心肌炎。

  • 影响因子:6.15
  • DOI:10.1016/j.ejca.2019.09.009
  • 作者列表:"Guo CW","Alexander M","Dib Y","Lau PKH","Weppler AM","Au-Yeung G","Lee B","Khoo C","Mooney D","Joshi SB","Creati L","Sandhu S
  • 发表时间:2020-01-01
Abstract

:Immune checkpoint inhibitors (ICI) and tyrosine kinase inhibitors (TKI) have transformed the management of many malignancies. Although rare, immune-mediated myocarditis presents unique clinical challenges due to heterogenous presentation, potential life-threatening consequences, and the time-critical need to differentiate it from other causes of cardiac dysfunction. Increasingly, TKI are being combined with ICI to promote immune modulation and improve efficacy. However, these combinations are associated with more toxicities. This series describes six patients with advanced melanoma who developed immune-mediated myocarditis while receiving an anti-PD-1 antibody or an anti-PD-L1 antibody plus a mitogen-activated protein kinase inhibitor. It provides a review of their heterogenous clinical presentations, investigational findings and treatment outcomes. Presentations ranged from asymptomatic cardiac enzyme elevation to death due to heart failure. We highlight the role of cardiac MRI (CMRI), a sensitive and non-invasive tool for the early detection and subsequent monitoring of myocardial inflammation. Five of the six patients exhibited CMRI changes characteristic of myocarditis, including mid-wall myocardial oedema and late gadolinium enhancement in a non-coronary distribution. Critically, two of these patients had normal findings on echocardiogram. Of the five patients who received immunosuppression, four recovered from myocarditis and one died of cardiac failure. The sixth patient improved with cardiac failure management alone. Three of the four patients responding to ICI derived long-term benefit. Clinical vigilance, prompt multimodal diagnosis and multidisciplinary management are paramount for the treatment of immune-mediated myocarditis.

摘要

免疫检查点抑制剂 (ICI) 和酪氨酸激酶抑制剂 (TKI) 已经改变了许多恶性肿瘤的管理。虽然罕见,免疫介导的心肌炎提出了独特的临床挑战,由于异质性的表现,潜在的危及生命的后果,和时间关键需要区分它与其他原因的心功能障碍。TKI越来越多地与ICI结合,促进免疫调节,提高疗效。然而,这些组合与更多的毒性相关。本系列描述了 6 例晚期黑色素瘤患者,他们在接受anti-PD-1 抗体或anti-PD-L1 抗体加丝裂原活化蛋白激酶抑制剂的同时发生免疫介导性心肌炎。它提供了对其异质性临床表现、研究结果和治疗结果的综述。表现范围从无症状的心肌酶升高到心力衰竭死亡。我们强调心脏MRI (CMRI) 的作用,CMRI是一种敏感和无创的早期检测和随后监测心肌炎症的工具。6 例患者中有 5 例表现出心肌炎特征性的CMRI改变,包括非冠状动脉分布的中壁心肌水肿和晚期钆增强。至关重要的是,其中 2 例患者超声心动图检查结果正常。5 例接受免疫抑制的患者中,4 例心肌炎痊愈,1 例死于心力衰竭。第 6 例患者单用心力衰竭治疗好转。对ICI有反应的 4 例患者中有 3 例获得长期获益。临床警惕、及时的多模式诊断和多学科管理对于免疫介导性心肌炎的治疗至关重要。

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皮肤肿瘤方向

皮肤肿瘤是发生在皮肤的细胞增生性疾病,是一种常见病。发生于皮内或皮下组织的新生物,种类很多,临床上分良性肿瘤和恶性肿瘤。恶性肿瘤可以不断增殖,引起转移,威胁生命,称为皮肤癌。

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