Valente Monica, Colucci Maura, Vegni Virginia, Croce Valentina, Bellan Cristiana, Rossi Giulia, Gibilisco Giulia, Frongia Francesco, Guazzo Raffaella, Ghiribelli Claudia, Bargagli Elena, Savelli Vinno, Ravara Matteo, Sani Tommaso, Simonetti Elena, Maio Michele, Calabrò Luana, Di Giacomo Anna Maria
Department of Oncology, Center for Immuno-Oncology, University Hospital of Siena, Siena, Italy.
Department of Medicine, Surgery and Neurosciences, University of Siena, Siena, Italy.
Onco Targets Ther. 2024 Aug 22;17:673-681. doi: 10.2147/OTT.S470892. eCollection 2024.
Treatment with immune-checkpoint inhibitors (ICIs) can be associated with a wide spectrum of immune-related adverse events (irAEs). Among irAEs, immune-mediated pneumonitis (im-PN) is a rare but potentially life-threatening side effect. TPrompt multidisciplinary diagnosis and effective management of im-PN may be essential to avoid severe complications and allowing resumation of therapy.
We collected a case series of skin (melanoma, cutaneous squamous cell carcinoma-CSCC), lung, and mesothelioma cancer patients (pts), treated with ICI at the Center for Immuno-Oncology University Hospital of Siena, Italy, and diagnosed with im-PN. Clinical and radiologic data were thoroughly collected, as well as bronchoalveolar lavage (BAL) samples; im-PN was graded using CTCAE v. 5.0. Radiological patterns were reported according to the leischner Society classification.
From January 2014 to February 2023, 1004 patients with melanoma (522), CSCC (42), lung (342) or mesothelioma (98) were treated with ICI (619 monotherapy; 385 combination). Among treated patients, 24 (2%) developed an im-PN and 58% were symptomatic. Im-PN were classified as grades G1 (10) and G2 (14). Prompt steroid treatment led to complete resolution of im-PN in 21 patients, with a median time to resolution of 14 weeks (range: 0.4-51). Twelve patients resumed ICI therapy once fully-recovered and 2 experienced a recurrence that completely resolved with steroids after resumption of treatment. Three radiologic patterns were identified: organizational pneumonia-like (67%), pulmonary eosinophilia (29%), and hypersensitivity pneumonitis (4%). Furthermore, BAL analysis performed in 8 (33%) patients showed an inflammatory lymphocytic infiltrate, predominantly consisting of foam cell-like macrophage infiltrates in 6 cases. Notably, transmission electron microscopy evaluation performed in 2 patients revealed a scenario suggestive of a drug-mediated toxicity.
Im-PN is a rare but challenging side effect of ICI therapy, with variable time of onset and with heterogeneous clinical and radiological presentations. A multidisciplinary assessment is mandatory to optimize the clinical management of im-PN.
免疫检查点抑制剂（ICI）治疗可能会伴有一系列广泛的免疫相关不良事件（irAE）。在irAE中，免疫介导的肺炎（im-PN）是一种罕见但可能危及生命的副作用。迅速进行多学科诊断和有效管理im-PN对于避免严重并发症并允许恢复治疗可能至关重要。
我们收集了一系列皮肤（黑色素瘤、皮肤鳞状细胞癌-CSCC）、肺癌和间皮瘤患者（pts）的病例，这些患者在意大利锡耶纳大学医院免疫肿瘤中心接受ICI治疗，并被诊断为im-PN。全面收集了临床和放射学数据以及支气管肺泡灌洗（BAL）样本；使用CTCAE v. 5.0对im-PN进行分级。根据莱施纳协会分类报告放射学模式。
从2014年1月至2023年2月，1004例黑色素瘤（522例）、CSCC（42例）、肺癌（342例）或间皮瘤（98例）患者接受了ICI治疗（619例单药治疗；385例联合治疗）。在接受治疗的患者中，24例（2%）发生了im-PN，58%有症状。im-PN分为G1级（10例）和G2级（14例）。及时的类固醇治疗使21例患者的im-PN完全缓解，缓解的中位时间为14周（范围：0.4-51周）。12例患者在完全康复后恢复了ICI治疗，2例复发，在恢复治疗后用类固醇完全缓解。确定了三种放射学模式：机化性肺炎样（67%）、肺嗜酸性粒细胞增多症（29%）和过敏性肺炎（4%）。此外，8例（33%）患者进行的BAL分析显示有炎性淋巴细胞浸润，6例主要由泡沫细胞样巨噬细胞浸润组成。值得注意的是，2例患者进行的透射电子显微镜评估显示出提示药物介导毒性的情况。
im-PN是ICI治疗罕见但具有挑战性的副作用，发病时间可变，临床和放射学表现各异。多学科评估对于优化im-PN的临床管理是必不可少的。
