PT  - JOURNAL ARTICLE
AU  - Moseley, Kendall F.
AU  - Naidoo, Jarushka
AU  - Bingham, Clifton O.
AU  - Carducci, Michael A.
AU  - Forde, Patrick M.
AU  - Gibney, Geoffrey T.
AU  - Lipson, Evan J.
AU  - Shah, Ami A.
AU  - Sharfman, William H.
AU  - Cappelli, Laura C.
TI  - Immune-related adverse events with immune checkpoint inhibitors affecting the skeleton: a seminal case series
AID  - 10.1186/s40425-018-0417-8
DP  - 2018 Dec 01
TA  - Journal for ImmunoTherapy of Cancer
PG  - 104
VI  - 6
IP  - 1
4099  - http://jitc.bmj.com/content/6/1/104.short
4100  - http://jitc.bmj.com/content/6/1/104.full
SO  - J Immunother Cancer2018 Dec 01; 6
AB  - Background The use of immune checkpoint inhibitors is increasing in cancer therapy today. It is critical that treatment teams become familiar with the organ systems potentially impacted by immune-related adverse events associated with these drugs. Here, we report adverse skeletal effects of immunotherapy, a phenomenon not previously described.Case presentations In this retrospective case series, clinical, laboratory and imaging data were obtained in patients referred to endocrinology or rheumatology with new fractures (n = 3) or resorptive bone lesions (n = 3) that developed while on agents targeting PD-1, CTLA-4 or both. The average age of patients was 59.3 (SD 8.6), and five were male. Cancer types included melanoma, renal cell carcinoma and non-small cell lung cancer. All fracture patients had vertebral compression, and two of the three had multiple fracture sites involved. Sites of resorptive lesions included the shoulder, hand and clavicle. Biochemically, elevated or high-normal markers of bone resorption were seen in five of the six patients. Erythrocyte sedimentation rate was elevated in three of the four patients where checked.Conclusions This case series represents the first description of potential skeletal adverse effects related to immune checkpoint inhibitors. These findings are important for providers caring for patients who experience musculoskeletal symptoms and may merit additional evaluation.Abbreviations:CTLA-4Cytotoxic T-lymphocyte associated protein 4CTXC-telopeptidesDXADual energy X-ray absorptiometryICIImmune checkpoint inhibitorIL-2Interleukin-2irAEsImmune-related adverse eventsOPGOsteoprotegerinPD-1Programmed death-1RANK-LReceptor Activator of Nuclear Factor-κB LigandSpASpondyloarthritis