PDL1 inhibitors may be associated with a lower risk of allograft rejection than PD1 and CTLA4 inhibitors: analysis of the WHO pharmacovigilance database

® (WHO's pharmacovigilance database) was queried for reports of AR involving CTLA4, PD1, or PDL1 inhibitors. Disproportionality analysis compares the proportion of reports with a specific adverse drug reaction (ADR) and a given drug to the proportion of reports with the same ADR and other drugs. A lower 95% confidence interval for the Information Component (IC) >0 suggests a signal. The comparative Reporting Odds Ratios (ROR) for AR, between PD1 and PDL1 inhibitors, was calculated.Results: We gathered 159 AR involving an ICI, especially nivolumab (73, 45.9%), mostly affecting kidneys (87, 54.7%). Median time to onset: 28 days. Fatal outcome: 36 reports (22.6%). ICI were significantly associated with AR: IC=1.7 [1.4;1.9]. Specifically, PD1 inhibitors yielded an IC of 2.0 [1.7;2.2] (152 reports observed compared to 38 expected). By contrast, the IC of PDL1 inhibitors was negative: -2.6 [-6.4;-1.0] (1 observed, 9 expected). The comparative ROR of PD1 compared to PDL1 inhibitors was 33.7 [4.7;240.9] (p=0.0005).onclusions: We confirm the association between ICI treatment and AR. Notably, PDL1 inhibitors showed surprisingly low AR reports compared to CTLA4 and PD1 inhibitors. Further prospective studies are warranted to confirm whether PDL1 inhibitors indeed reduce AR risk compared to other ICI.