Risk monitoring and pharmacovigilance of programmed cell death protein 1 / programmed cell death 1 ligand 1 in cancer patients after solid organ transplantation

Long Mei; Sa Li; Qianqian Fan; Bin Zhao; Dan Mei; Roxane Took; Jiancun Zhen

doi:10.1016/j.therap.2022.10.001

Risk monitoring and pharmacovigilance of programmed cell death protein 1 / programmed cell death 1 ligand 1 in cancer patients after solid organ transplantation

Therapie. 2023 Jul-Aug;78(4):385-392. doi: 10.1016/j.therap.2022.10.001. Epub 2022 Oct 11.

Authors

Long Mei¹, Sa Li¹, Qianqian Fan², Bin Zhao², Dan Mei², Roxane Took³, Jiancun Zhen⁴

Affiliations

¹ Department of Pharmacy, Beijing Jishuitan Hospital, Xicheng District Xinjiekou No. 31, East Beijing 100035, PR China.
² Department of Pharmacy, Peking Union Medical College Hospital, Beijing 100730, PR China.
³ Pharmacy Practice, St. Louis College of Pharmacy, St. Louis MO 63110-1088, United States.
⁴ Department of Pharmacy, Beijing Jishuitan Hospital, Xicheng District Xinjiekou No. 31, East Beijing 100035, PR China. Electronic address: zhenjiancun@163.com.

PMID: 36481226
DOI: 10.1016/j.therap.2022.10.001

Abstract

Introduction: Several medications are available for the treatment of cancer, and monoclonal antibodies that target PD-1 and PD-L1 represent first-line options for cancer. PD-1 promotes the ability of the immune system to recognize and attack cancer cells by activating T cells. PD-1 also activates the autoimmune system. This activation causes healthy cells in the body to be attacked by the immune system, resulting in immune-related adverse events (irAE). The objective of this study was to comprehensively evaluate the adverse events of rejection reactions in real-world solid organ transplant patients using monoclonal antibodies that target PD-1/PD-L1.

Methods: Data from 2016-2021 were extracted from the U.S. Food and Drug Administration(FDA) Adverse Reporting System (FAERS) to describe the rejection reaction in patients with solid organ transplantation cases after using PD-1/PD-L1 inhibitors approved by the FDA. The reporting odds ratio (ROR) with 95% confidence interval (CI) for rejection reaction was calculated for each PD-1/PD-L1 inhibitor. A disproportionality signal was defined when the lower limit of 95% CI>1.

Results: The FAERS database recorded 11,935 adverse events related to solid organ transplantation. Among these reports, 117 showed that various PD-1/PD-L1 inhibitors exhibited a strong correlation with solid organ transplantation rejection. The 3 medicines with the incidence of rejection reaction include avelumab (1), nivolumab (79) and pembrolizumab (37). The average time of solid organ transplantation rejection associated with PD1 / PD-L1 inhibitors was 40.64 days. Of those patients who experienced solid organ transplant rejection, a total of 24.79% died.

Conclusion: This study found that PD-1/PD-L1 inhibitor use in patients with solid organ transplantation was associated with donor organ rejection. This information serves as a pharmacovigilance signal that we need to continue to track in the real world.

Keywords: FAERS; PD-1/PD-L1 inhibitors; Rejection reaction; Solid organ transplantation.