Allograft Rejection Following the Use of Immune Checkpoint Inhibitors: Exploring the FDA Adverse Event Reporting System

Immune checkpoint inhibitors (ICIs) are widely used in different tumors due to their remarkable survival benefits, but efficacy and safety data are lacking in solid organ transplant recipients (SOTRs) who were treated with ICIs. The objective of our study was to assess the main features of transplant rejection after ICIs usage, and evaluate the associations between transplant rejection and ICIs in the US FDA Adverse Event Reporting System (FAERS) database. The characteristics of transplant rejection associated with ICIs were described, and the time onset of rejection after ICI initiation, and the fatality rate of different ICI regimens were calculated and compared with each other. 168 patients with allograft rejection after ICI usage were identified. Anti-PD-1 agents accounts for the majority of transplant rejections with 144 cases (85.7%), whereas anti-PD-L1 (Avelumab) and Anti-CTLA4 (Ipilimumab) were one case and six cases respectively, and 17 cases of transplant rejection occurred in combination therapy with two kinds of ICIs. We first report the largest and most extensive pharmacovigilance study on transplant rejection in patients with ICIs treatment derived from FAERS database. Further studies and multi-center registration of SOTRs with ICIs are needed to optimize a safe and effective use of ICIs in allograft patients.