Liang Xiuju, Guan Yaping, Zhang Bicheng, Liang Jing, Wang Baocheng, Li Yan, Wang Jun
Department of Oncology, No. 960 Hospital, The People's Liberation Army, Jinan, China.
Department of Respiratory Medicine, Shandong Thoracic Diseases Hospital, Jinan, China.
Front Oncol. 2019 Dec 18;9:1437. doi: 10.3389/fonc.2019.01437. eCollection 2019.
Combination therapy with programmed cell death protein-1 (PD-1) and programmed cell death ligand-1 (PD-L1) inhibitors might be viewed as a promising therapeutic strategy for resistant lung cancer, and it is becoming common that a second PD-1/PD-L1 inhibitor might be used following progression on previous PD-1/PD-L1 inhibitor. However, a subgroup of patients will experience various autoimmune toxicities, termed as immune-related adverse events (irAEs), that occur as a result of on-target and off-tumor inflammation. In this report, we presented a patient with small cell lung cancer who received different PD-1/PD-L1 inhibitors during the course of disease progression. This patient experienced radiation-related pneumonitis, immune-related pneumonitis, as well as concomitant bacterial pneumonia. In particular, this patient developed immune-related pneumonitis with a second PD-1 inhibitor when she had a progressive disease on previous PD-L1 inhibitor. This patient was initially responsive to steroid treatment, but rapidly develop more severe pneumonitis and concomitant bacterial pneumonia with no response to antibiotics and steroid treatment. Finally, this patient got a good clinical response when receiving additional immunosuppressive medications infliximab and mycophenolate mofetil. Patients with a history of radiation-induced pneumonitis and treated with sequential different PD-1/PD-L1 inhibitors have a relative high risk to develop high-grade or steroid-resistant pneumonitis, and additional immunosuppressive medications should be used earlier when severe pulmonary toxicity occurs.
程序性细胞死亡蛋白-1(PD-1)和程序性细胞死亡配体-1(PD-L1)抑制剂联合治疗可能被视为耐药肺癌的一种有前景的治疗策略,并且在先前的PD-1/PD-L1抑制剂治疗进展后使用第二种PD-1/PD-L1抑制剂正变得越来越普遍。然而,有一部分患者会出现各种自身免疫毒性,称为免疫相关不良事件(irAEs),这些事件是由靶向和肿瘤外炎症引起的。在本报告中,我们介绍了一名小细胞肺癌患者,该患者在疾病进展过程中接受了不同的PD-1/PD-L1抑制剂治疗。该患者经历了放射性肺炎、免疫相关肺炎以及合并细菌性肺炎。特别是,该患者在先前的PD-L1抑制剂治疗出现疾病进展时,使用第二种PD-1抑制剂后发生了免疫相关肺炎。该患者最初对类固醇治疗有反应,但迅速发展为更严重的肺炎并合并细菌性肺炎,对抗生素和类固醇治疗均无反应。最后,该患者在接受额外的免疫抑制药物英夫利昔单抗和霉酚酸酯治疗后获得了良好的临床反应。有放射性肺炎病史且接受序贯不同PD-1/PD-L1抑制剂治疗的患者发生高级别或类固醇耐药性肺炎的风险相对较高,当发生严重肺部毒性时应更早使用额外的免疫抑制药物。