Service de pneumologie, centre de compétence maladies pulmonaires rares, hôpital européen Georges-Pompidou, AP-HP, 75000 Paris, France.
Service de pneumologie, centre de compétence maladies pulmonaires rares, hôpital européen Georges-Pompidou, AP-HP, 75000 Paris, France.
Therapie. 2023 May-Jun;78(3):267-278. doi: 10.1016/j.therap.2022.05.008. Epub 2022 Jun 8.
Mammalian target of rapamycin (mTOR) inhibitors-associated pneumonitis (mTOR-IP) has long been described in solid organ recipients (T) patients but more recently in cancer (K) patients. Its overall characteristics have never been compared between these 2 populations. The aim of this study was to compare them in terms of presentation, severity and outcome in T and in K patients.
We carried out a retrospective study in a single French tertiary center. Four databases were used to ensure the exhaustive collection of all mTOR-IP cases between 2001 and 2020. All clinical, biological, radiological, pathological and outcome data were reviewed.
Thirty-nine patients with mTOR-IP were diagnosed during this period, 24T and 15K patients. The average dosage of everolimus and sirolimus was 2,65mg (±1,78) and 2,75mg (±0,96) in T patients, respectively, versus 8,75mg (±2,26) for everolimus in K patients. The overall prevalence of mTOR-IP was 6.4% with a median time of occurrence of 7 months [IQR 3-35 months]. mTOR-IP were significantly more frequent (P<0.001) and occurred earlier (P<0.001) in cancer patients. No clinical, functional, radiological, pathological nor outcome differences were otherwise observed between the 2 groups. Average everolimus blood levels at the time of mTOR-IP diagnosis were in the range of recommended therapeutic values.
Our study shows that mTOR-IP is comparable in terms of presentation in T and in K patients but that it occurs significantly earlier after drug introduction in the latter. This raises questions as to the potential role of the higher doses used in K patients as well as that of co-treatments in the pathogeny of the disease.
哺乳动物雷帕霉素靶蛋白（mTOR）抑制剂相关肺炎（mTOR-IP）在实体器官受者（T）患者中早已被描述，但在最近的癌症（K）患者中也有报道。但这两种人群的总体特征从未进行过比较。本研究旨在比较这两种人群在表现、严重程度和结局方面的差异。
我们在法国的一家三级中心进行了一项回顾性研究。使用四个数据库来确保在 2001 年至 2020 年期间收集所有 mTOR-IP 病例。回顾了所有的临床、生物学、放射学、病理学和结局数据。
在此期间共诊断出 39 例 mTOR-IP 患者，其中 24 例为 T 患者，15 例为 K 患者。T 患者中依维莫司和西罗莫司的平均剂量分别为 2.65mg（±1.78）和 2.75mg（±0.96），而 K 患者中依维莫司的平均剂量为 8.75mg（±2.26）。mTOR-IP 的总体患病率为 6.4%，中位发生时间为 7 个月[IQR 3-35 个月]。癌症患者中 mTOR-IP 明显更常见（P<0.001），发生时间更早（P<0.001）。两组之间在临床、功能、放射学、病理学或结局方面无差异。mTOR-IP 诊断时平均依维莫司血药水平处于推荐治疗范围。
我们的研究表明，mTOR-IP 在 T 患者和 K 患者中的表现相似，但在后者中，药物引入后发生时间明显更早。这引发了一些问题，即 K 患者中使用的较高剂量以及联合治疗在疾病发病机制中的潜在作用。
