*Department of Surgery, Section of Surgical Oncology †Department of Internal Medicine, Section of Pulmonary, Critical Care and Sleep Medicine ‡Department of Internal Medicine, Section of Medical Oncology Departments of §Dermatology ∥Pathology, Yale University School of Medicine, New Haven, CT.
J Immunother. 2017 Oct;40(8):307-311. doi: 10.1097/CJI.0000000000000181.
Immune checkpoint inhibitors represent the newest treatment for stage IV melanoma. These agents are generally well tolerated, however severe immune-related adverse effects have been noted in a small, but clinically significant percentage of patients. Specifically, sarcoidosis is a known potential complication following anti-CTLA-4 therapy. We present 2 cases of pulmonary and cutaneous sarcoidosis developing in patients with stage IV melanoma. Both patients were treated with ipilimumab and anti-PD-1 therapy, and both experienced good oncologic responses to treatment; neither had evidence of preexisting sarcoidosis. Of note, both patients developed sarcoidosis only after undergoing immune checkpoint inhibitor therapy. In 1 patient, sarcoidosis developed after initiation of anti-PD-1 therapy, 3 months after the last dose of anti-CTLA-4 monotherapy, suggesting a synergistic immune dysmodulating effect of both checkpoint inhibitors. Ultimately, both patients' symptoms and radiologic findings resolved with corticosteroid treatment, and both patients have tolerated retreatment with PD-1 inhibitors. Sarcoidosis is a rare complication of immune checkpoint inhibitors and can manifest with severe pulmonary manifestations. However, sarcoidosis in this setting is responsive to corticosteroids and does not necessarily recur with retreatment. It is yet unclear whether the development of sarcoidosis in these patients represents unmasking of preexisting autoimmune tendencies or is a marker of oncologic response.
免疫检查点抑制剂是治疗 IV 期黑色素瘤的最新方法。这些药物通常具有良好的耐受性，但在一小部分具有临床意义的患者中，已注意到严重的免疫相关不良反应。具体而言，结节病是抗 CTLA-4 治疗后已知的潜在并发症。我们报告了 2 例 IV 期黑色素瘤患者发生的肺和皮肤结节病。这 2 例患者均接受了伊匹单抗和抗 PD-1 治疗，并且均对治疗有良好的肿瘤反应；两者均无结节病的前期证据。值得注意的是，这 2 例患者仅在接受免疫检查点抑制剂治疗后才发生结节病。1 例患者在接受抗 PD-1 治疗 3 个月后，即在最后一次 CTLA-4 单药治疗后，出现了结节病，这表明两种检查点抑制剂具有协同的免疫调节作用。最终，这 2 例患者的症状和影像学发现均通过皮质类固醇治疗得到缓解，且均耐受 PD-1 抑制剂的再治疗。结节病是免疫检查点抑制剂的罕见并发症，可表现为严重的肺部表现。然而，在这种情况下的结节病对皮质类固醇有反应，并且不一定会随着再治疗而复发。目前尚不清楚这些患者的结节病的发生是代表先前存在的自身免疫倾向的显现，还是肿瘤反应的标志物。
