Pantano Francesco, Tramontana Flavia, Iuliani Michele, Leanza Giulia, Simonetti Sonia, Piccoli Alessandra, Paviglianiti Annalisa, Cortellini Alessio, Spinelli Gian Paolo, Longo Umile Giuseppe, Strollo Rocky, Vincenzi Bruno, Tonini Giuseppe, Napoli Nicola, Santini Daniele
Medical Oncology Department, Campus Bio-Medico University of Rome, Rome, Italy.
Department of Medicine, Unit of Endocrinology and Diabetes, Università Campus Bio-Medico di Roma, Rome, Italy.
J Bone Oncol. 2022 Oct 28;37:100459. doi: 10.1016/j.jbo.2022.100459. eCollection 2022 Dec.
Immune checkpoint inhibitors (ICIs) has revolutionized the treatment of different advanced solid tumors, but most patients develop severe immune-related adverse events (irAEs). Although a bi-directional crosstalk between bone and immune systems is widely described, the effect of ICIs on the skeleton is poorly investigated. Here, we analyze the changes in plasma levels of type I collagen C-terminal telopeptide (CTX-I) and -terminal propeptide of type I procollagen (PINP), reference makers of bone turnover, in patients treated with ICIs and their association with clinical outcome. A series of 44 patients affected by advanced non-small cell lung cancer or renal cell carcinoma, without bone metastases, and treated with ICIs as monotherapy were enrolled. CTX-I and PINP plasma levels were assessed at baseline and after 3 months of ICIs treatment by ELISA kits. A significant increase of CTX-I with a concomitant decreasing trend towards the reduction of PINP was observed after 3 months of treatment. Intriguingly, CTX-I increase was associated with poor prognosis in terms of treatment response and survival. These data suggest a direct relationship between ICIs treatment, increased osteoclast activity and potential fracture risk. Overall, this study reveals that ICIs may act as triggers for skeletal events, and if confirmed in larger prospective studies, it would identify a new class of skeletal-related irAEs.
免疫检查点抑制剂（ICIs）彻底改变了不同晚期实体瘤的治疗方式，但大多数患者会出现严重的免疫相关不良事件（irAEs）。尽管骨骼与免疫系统之间的双向串扰已被广泛描述，但ICIs对骨骼的影响却鲜有研究。在此，我们分析了接受ICIs治疗的患者血浆I型胶原C端肽（CTX-I）和I型前胶原N端前肽（PINP）水平的变化，这两种物质是骨转换的参考指标，以及它们与临床结局的关联。我们纳入了44例患有晚期非小细胞肺癌或肾细胞癌、无骨转移且接受ICIs单药治疗的患者。通过ELISA试剂盒在基线和ICIs治疗3个月后评估CTX-I和PINP的血浆水平。治疗3个月后，观察到CTX-I显著升高，同时PINP有下降趋势。有趣的是，就治疗反应和生存而言，CTX-I升高与预后不良相关。这些数据表明ICIs治疗、破骨细胞活性增加与潜在骨折风险之间存在直接关系。总体而言，本研究表明ICIs可能是骨骼事件的触发因素，如果在更大规模的前瞻性研究中得到证实，将确定一类新的骨骼相关irAEs。
