(27) Sarcoidosis Associated with Pembrolizumab Alone or in combination with chemotherapy agents: A Pharmacovigilance Analysis of the FDA Adverse Event Reporting System (FAERS)

Background: Pembrolizumab has been used as a monotherapy or in combination with chemotherapy drugs such as Carboplatin, Cisplatin, Paclitaxel, Pemetrexed, and Etoposide for renal cell carcinoma, merkel cell carcinoma, endometrial cancer, and non-small cell lung cancer. To our knowledge, the risk of sarcoidosis with combination therapies of pembrolizumab has not yet been explored. 

OBJECTIVES: To quantify the signal strength of sarcoidosis with Pembrolizumab in combination with other classes of drugs such as Folate antagonists, Pyrimidine antagonists, Taxanes, and Tyrosine kinase inhibitors. 

METHODS: Open Vigil 2.1 was utilized for the case/non-case retrospective disproportionality study in the publicly accessible FAERS database (2004Q1-2022Q3). The preferred term for the study was "sarcoidosis," and the drugs included in the analysis were ‘Pembrolizumab’, ‘Axitinib’, ‘Lenvatinib’, ‘Pemetrexed’, ‘Cisplatin’, ‘Carboplatin’, ‘Fluorouracil’, and ‘Paclitaxel’. The data mining algorithm used for the analysis was Reporting Odds Ratio (ROR) and Proportional Reporting Ratio (PRR). The threshold for a signal was defined as ROR-1.96SE>1 and PRR ≥2 with an accompanying X2 value of 4 or above. 

Results: FAERS database had a total of 2186 reports associated with sarcoidosis, out of which 41 reports were associated with pembrolizumab. The crude ROR value of pembrolizumab was 8.906 (95% CI 6.536-12.133). Amongst all the existing combinations of pembrolizumab, the signal strength was found to be highest with the combination of pembrolizumab, carboplatin, and pemetrexed [ ROR 40.128 (95% CI 23.675-68.018)]. On gender stratification, the ROR values revealed males to be 1.22 times at higher risk than females. The other combinations of Pembrolizumab with Axitinib, Lenvatinib, and Paclitaxel Fluorouracil did not demonstrate higher ROR values suggestive of no increased risk. 

Conclusion: Patients treated with pembrolizumab monotherapy or a combination of Pembrolizumab, Carboplatin, and Pemetrexed may be at increased risk of sarcoidosis as was depicted in our study, while a causal relationship cannot be proven. Hence, further epidemiological studies are required to validate the findings.