Department of Internal Medicine, Division of Medical Oncology, University Hospital Basel, Basel, Switzerland.
Division of Pneumology and Pulmonary Cell Research, University Hospital Basel, Basel, Switzerland.
J Immunother Cancer. 2018 Sep 3;6(1):85. doi: 10.1186/s40425-018-0400-4.
The development of pulmonary immune-related adverse events (irAEs) in patients undergoing PD-(L)1 targeted checkpoint inhibitors are rare, but may be life-threatening. While many published articles and guidelines are focusing on the presentation and upfront treatment of pulmonary irAEs, the strategy in patients with late-onset pneumonia that are resistant to commonly used immunosuppressive drugs remains unclear.
Here, we report the successful treatment of a mycophenolate-resistant organizing pneumonia (OP) with infliximab in a patient with metastatic melanoma after PD-1 blockade. The patient received two years of PD-1 targeted immunotherapy when he developed multiple nodular lung lesions mimicking a metastatic progression. However, wedge resection of these lesions showed defined areas of OP, which responded well to corticosteroids. Upon tapering, new foci of OP developed which were resistant to high-dose steroids and mycophenolate treatment. The TNFα antagonist infliximab led to a rapid and durable regression of the inflammatory lesions.
This case describes a not well-studied situation, in which a mycophenolate-resistant PD-1 blocker-associated pneumonitis was successfully treated with a TNFα neutralizing antibody. The outcome of this case suggests that infliximab might be the preferable option compared to classical immunosuppressants in the case of steroid-resistant/-dependent late onset pulmonary irAEs.
接受 PD-(L)1 靶向检查点抑制剂治疗的患者发生肺部免疫相关不良事件(irAEs)的情况较为罕见,但可能危及生命。尽管许多已发表的文章和指南都侧重于肺部 irAEs 的表现和一线治疗,但对于对常用免疫抑制剂耐药的迟发性肺炎患者的治疗策略仍不明确。
在这里,我们报告了一例转移性黑色素瘤患者在 PD-1 阻断后使用英夫利昔单抗成功治疗霉酚酸酯耐药性机化性肺炎(OP)的病例。该患者在接受了两年的 PD-1 靶向免疫治疗后,出现了多个类似转移进展的结节性肺部病变。然而,对这些病变进行楔形切除后显示出明确的 OP 区域,对皮质类固醇反应良好。在逐渐减少剂量时,新出现的 OP 病灶对大剂量类固醇和霉酚酸酯治疗耐药。TNFα 拮抗剂英夫利昔单抗导致炎症病变迅速和持久消退。
本病例描述了一种研究较少的情况,即霉酚酸酯耐药的 PD-1 阻滞剂相关肺炎在使用 TNFα 中和抗体后得到成功治疗。该病例的结果表明,在类固醇耐药/依赖的迟发性肺部 irAEs 情况下,英夫利昔单抗可能是比传统免疫抑制剂更优选的方案。