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 N-terminal propeptide of type I procollagen (PINP), reference makers of bone turnover, in patients treated with ICIs and their associ-ation 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 pro-spective studies, it would identify a new class of skeletal-related irAEs.

Changes in bone turnover markers in patients without bone metastases receiving immune checkpoint inhibitors: An exploratory analysis

Pantano, Francesco;Tramontana, Flavia;Leanza, Giulia;Longo, Umile Giuseppe;Strollo, Rocky;Vincenzi, Bruno;Tonini, Giuseppe;Napoli, Nicola;Santini, Daniele
2022-01-01

Abstract

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 N-terminal propeptide of type I procollagen (PINP), reference makers of bone turnover, in patients treated with ICIs and their associ-ation 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 pro-spective studies, it would identify a new class of skeletal-related irAEs.
2022
APRIL, a proliferation-inducing ligand; Bone health; CT-scan, Computed Tomography Scan; CTX-I, type I collagen C-Terminal telopeptide; ECOG, Eastern Cooperative Oncology Group; ELISA, Enzyme-Linked Immunosorbent Assay; ICIs, Immune Checkpoint Inhibitors; IFN-γ, Interferon-γ; IL-6, Interleukin-6; Immune checkpoint inhibitors (ICIs); N-terminal propeptide of type I procollagen (PINP); NSCLC, Non-Small Cell Lung Cancer; OPG, Osteoprotegerin; OS, Overall Survival; PD-L1, Programmed cell Death Ligand 1; PINP, N-terminal Propeptide of type I Procollagen; RANKL, nuclear factor kappa-B ligand; RCC, Renal Cell Carcinoma; RECIST, Response Evaluation Criteria in Solid Tumors; T0, Time 0; T1, Time 1; TNF-α, Tumor Necrosis Factor-α; TTF, Time to Treatment Failure; Th17, T helper 17; Type I Collagen C-Terminal Telopeptide (CTX-I); irAEs, Immune-Related Adverse Events
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.12610/75723
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