Bone fracture as a novel immune‐related adverse event with immune checkpoint inhibitors: Case series and large‐scale pharmacovigilance analysis. Issue 3 (4th May 2021)

• Record Type: Journal Article
• Authors: Filippini, Daria Maria; Gatti, Milo; Di Martino, Vito; Cavalieri, Stefano; Fusaroli, Michele; Ardizzoni, Andrea; Raschi, Emanuel; Licitra, Lisa
• Is Part Of: International journal of cancer. Volume 149:Issue 3(2021)
• Page Start: 675
• Page End: 683
• Publication Date: 2021-05-04
• Subjects: disproportionality analysis -- immune checkpoint inhibitors -- skeletal immune‐related adverse events -- vertebral fracture; Cancer -- Periodicals; Cancer -- Prevention -- Periodicals; 616.994
• DOI: 10.1002/ijc.33592
• Languages: English
• ISSNs: 0020-7136

Abstract

Abstract: Although immune checkpoint inhibitors (ICIs) are associated with different immune‐related adverse events (irAEs), the potential effect on the skeleton is poorly defined albeit biologically plausible and assessable through pharmacovigilance. We described a case series of patients experiencing skeletal fractures while on ICIs at the National Cancer Institute of Milan. To better characterize the clinical features of skeletal irAEs reported with ICIs, we queried the FDA Adverse Event Reporting System (FAERS) and performed disproportionality analysis by means of reporting odds ratios (RORs), deemed significant by a lower limit of the 95% confidence interval (LL95% CI) > 1. Bone AEs emerging as significant were scrutinized in terms of demographic and clinical data, including concomitant irAEs or drugs affecting bone resorption or causing bone damage. Four patients with skeletal events while on ICIs were included in our case series, of which three exhibited vertebral fractures. In FAERS, 650 patients with bone and joint injuries and treated with ICIs were retrieved, accounting for 822 drug‐event pairs. Statistically significant ROR was found for eight, two and one bone AEs respectively with PD‐1, PD‐L1 and CTLA‐4 inhibitors, being pathological fracture (N = 46; ROR = 3.17; LL95%CI = 2.37), spinal compression fracture (42; 2.51; 1.91), and femoral neck fracture (26; 2.38; 1.62) the most common. Concomitant irAEs or drugs affecting bone metabolism were poorly reported. The increased reporting of serious vertebral fractures in patients without concomitant irAEs and no apparent preexisting risk factors could suggest a possible cause‐effect relationship and calls for close clinical monitoring and implementation of dedicated guidelines. Abstract : What's new? Immune checkpoint inhibitors (ICIs), while potentially improving cancer patient survival, are associated with sometimes severe immune‐related adverse events. While these events affect all host tissues, little is known about their impact on bone in particular. Here, the authors investigated accounts of bone and joint injuries among patients taking ICIs, using clinical data and reports submitted to a pharmacovigilance database. Analyses show that ICIs may precipitate adverse skeletal events and reveal an increased reporting of serious vertebral fractures in patients lacking pre‐existing risk factors. The findings suggest that risk stratification and monitoring for skeletal lesions in patients taking ICIs is warranted.