Duchemann B, Didier M, Pailler M-C, Brillet P-Y, Kambouchner M, Uzunhan Y, Freynet O, Chouahnia K, Zelek L, Nunes H
Oncologie, Assistance publique-Hôpitaux de Paris, 25, rue de Stalingrad, 93000 Bobigny, France; Laboratoire d'immunomonitoring en oncologie Villejuif, 94800 Gustave Roussy, Île-de-France, France.
Pneumologie, Assistance publique-Hôpitaux de Paris, 93000 Bobigny, France.
Rev Mal Respir. 2019 Feb;36(2):209-213. doi: 10.1016/j.rmr.2018.11.001. Epub 2019 Jan 24.
Anti-PD1 immunotherapies have become an essential treatment for bronchial cancer. According to published studies, PD1 and PD-L1 inhibitors have a better toxicity profile than chemotherapy. Nevertheless, some immune related toxicities can be potentially severe, such as induced interstitial lung disease (ILD). Currently, ILD patients are excluded from clinical trials using immunotherapy in lung cancer. IPF is the most frequent and severe form of ILD. Lung cancer represents a major complication of this disease and to date few data exist on the safety of immunotherapy in this context. We report 3 cases of IPF with lung cancer treated by nivolumab. All had a clinically mild to moderate IPF. The patients had received at least one line of chemotherapy before nivolumab and had progressive, metastatic lung cancer. Two patients experienced rapid cancer progression without immune toxicities. The third had a partial response but developed grade III immune colitis that led to discontinuation of the treatment. None developed lung toxicity or worsening of IPF on CT during follow-up, and death was always related to progression of the cancer. In our series of three patients with IPF, nivolumab was well tolerated with regard to their pulmonary condition. As inflammation and autoimmunity are probably marginal mechanisms in the pathogenesis of IPF, we do not believe that the presence of IPF should definitely disqualify potential candidates for treatment with nivolumab. Decisions should be taken, case-by-case, in selected patients without severe IPF and with no evidence of autoimmunity. In view of the epidemiology of lung cancer in IPF and the critical role of immunotherapy in the management of lung cancer, studies of prospective cohorts are urgently needed in this population.
抗PD1免疫疗法已成为支气管癌的重要治疗方法。根据已发表的研究，PD1和PD-L1抑制剂的毒性特征优于化疗。然而，一些免疫相关毒性可能潜在严重，如诱发的间质性肺疾病（ILD）。目前，ILD患者被排除在肺癌免疫治疗的临床试验之外。特发性肺纤维化（IPF）是ILD最常见和最严重的形式。肺癌是这种疾病的主要并发症，迄今为止，关于在这种情况下免疫治疗安全性的数据很少。我们报告了3例接受纳武单抗治疗的IPF合并肺癌患者。所有患者的IPF在临床上均为轻度至中度。这些患者在接受纳武单抗治疗前至少接受过一线化疗，且患有进展性转移性肺癌。两名患者癌症快速进展，未出现免疫毒性。第三名患者部分缓解，但出现了III级免疫性结肠炎，导致治疗中断。随访期间，所有患者在CT上均未出现肺部毒性或IPF恶化，死亡均与癌症进展有关。在我们这组3例IPF患者中，纳武单抗对其肺部状况耐受性良好。由于炎症和自身免疫可能是IPF发病机制中的边缘机制，我们认为IPF的存在不一定应排除纳武单抗治疗的潜在候选者。对于没有严重IPF且无自身免疫证据的选定患者，应逐案做出决定。鉴于IPF中肺癌的流行病学情况以及免疫治疗在肺癌管理中的关键作用，迫切需要对这一人群进行前瞻性队列研究。
