OBJECTIVES Treatment options for malignant pleural mesothelioma (MPM) are limited but some studies on immune checkpoint inhibitors (ICIs) in MPM have reported antitumor activity. Very little is known about immune-related predictive factors. MATERIALS AND METHODS Here we report the case of a 45-year-old woman presenting with dyspnea and evidence of pleural effusion. She was diagnosed with malignant epithelioid pleural mesothelioma with brain metastasis and peritoneal carcinosis, refractory to initial standard chemotherapy treatment. Because of high PDL1 expression (100 %), she was treated with the anti-PD1 agent, pembrolizumab. RESULTS Chemotherapy with cisplatin and pemetrexed was started, imaging studies showing stable disease after 3 treatment cycles. The patient underwent pleural decortication but rapidly progressed and thus started chemotherapy with carboplatin and gemcitabine. After 2 cycles she experienced seizures caused by a brain metastasis. This secondary lesion was surgically removed and confirmed as a metastasis from mesothelioma. Samples from both the primary tumor and the metastasis were molecularly characterized, the pleural sample proving ALK-positive and the brain sample, ALK-negative. PD-L1 was positive in 10 % of tumor cells in the pleural biopsy and 100 % in the brain lesion. Next generation sequencing analysis was negative for both samples. It was decided to start alectinib. Disease progression (peritoneal carcinosis and liver metastases) was documented after one month followed by complete bowel obstruction and recurrence in the site of the brain surgery. Alectinib was stopped and supportive care begun with parenteral nutrition via nasogastric tube. Pembrolizumab was started and after 15 days the patient's condition had significantly improved, enabling recanalization and restoration of enteral nutrition. Imaging displayed complete response of the brain metastasis, peritoneal carcinosis, bone lesions and mediastinal nodal metastases. A partial response was documented in the pleural and pulmonary nodules, with stable liver metastases. The patient is still undergoing immunotherapy and has no cancer-related symptoms. CONCLUSIONS Our findings indicate that the use of immunotherapy in MPM warrants further investigation. Furthermore, the impressive clinical response obtained by our patient suggests that immune checkpoint inhibitors could help in the management of the disease after the failure of other treatments.

中文翻译：

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具有高克隆PD-L1表达和EML4-ALK重排的上皮样间皮瘤对抗PD-1治疗的临床反应令人印象深刻。

目的恶性胸膜间皮瘤（MPM）的治疗选择有限，但是一些关于MPM中免疫检查点抑制剂（ICIs）的研究报告了抗肿瘤活性。关于免疫相关的预测因素知之甚少。材料与方法在这里，我们报道了一名45岁的女性，该患者出现呼吸困难和胸腔积液的证据。她被诊断出患有恶性上皮样胸膜间皮瘤，并伴有脑转移和腹膜癌，对最初的标准化疗无效。由于PDL1高表达（100％），她接受了抗PD1药物pembrolizumab的治疗。结果开始使用顺铂和培美曲塞进行化学疗法，影像学研究显示3个治疗周期后疾病稳定。患者接受胸膜剥脱术，但进展迅速，因此开始使用卡铂和吉西他滨进行化疗。2个周期后，她经历了因脑转移引起的癫痫发作。通过外科手术切除该继发性病变，并确认其为间皮瘤转移。对来自原发性肿瘤和转移灶的样本进行分子表征，胸膜样本证明ALK阳性，脑样本证明ALK阴性。胸膜活检中10％的肿瘤细胞和脑病变中100％的PD-L1阳性。两种样品的下一代测序分析均为阴性。决定开始使用艾乐替尼。一个月后记录了疾病进展（腹膜癌变和肝转移），随后完全肠梗阻和脑外科手术部位复发。停用艾乐替尼，并开始通过鼻胃管进行肠外营养以支持治疗。开始使用Pembrolizumab，15天后患者的病情明显好转，可以再次通肠并恢复肠内营养。影像学检查显示脑转移，腹膜癌，骨病变和纵隔淋巴结转移完全反应。胸膜和肺结节有部分反应，肝转移稳定。该患者仍在接受免疫治疗，没有癌症相关症状。结论我们的发现表明，在MPM中使用免疫疗法值得进一步研究。此外，