Immune checkpoint inhibitor-related reproductive adverse effects: A pharmacovigilance analysis based on the FAERS database.

e14707 Background: There exists a critical need to systematically understand the extent and magnitude of immune checkpoint inhibitor (ICI)-related reproductive adverse effects, which may not only pose long-term implications for patients who may desire future fertility, but also impact the quality of life. We aim to better understand this underexplored area. Methods: Our focus was on ICIs approved by the FDA as of June 31, 2023, including anti-PD-1 agents (nivolumab, pembrolizumab, cemiplimab, dostarlimab, retifanlimab), anti-PD-L1 agents (atezolizumab, avelumab, durvalumab), anti-CTLA-4 agents (ipilimumab, tremelimumab), and an anti-LAG-3 agent (relatlimab). We analyzed 13,702,373 cases from January 1, 2015, to June 30, 2023. We included adverse reactions under the 'Reproductive system and breast disorders' category in the SOC (System Organ Classes). For signal detection, we used the reporting odds ratio (ROR) method. Results: We identified 133,512 patients administered with ICIs, among whom 568 reported irRAEs. Abnormal spermatogenesis (ROR025: 7.91), scrotal irritation (ROR025: 3.83), scrotal oedema (ROR025: 1.90), perineal rash (ROR025: 1.38), prostatitis (ROR025: 1.25), acquired phimosis (ROR025: 1.20), and scrotal erythema (ROR025: 1.08) in males and genital tract fistula in females (ROR025: 2.72) were detected as significant irRAEs. Among them, the most commonly reported irRAEs were prostatitis (n=29), scrotal oedema (n=12), and abnormal spermatogenesis (n=6) in males and genital tract fistula (n=34) in females. Male patients had a lower risk compared to females (OR=0.68 [0.57-0.81], p<0.0001). There was no marked difference between the patients on polytherapy vs. monotherapy (OR=0.90 [0.71-1.13], p=0.36). PD-1 inhibitors pose the greatest risk when compared with CTLA-4 inhibitors (OR=1.65 [1.05-2.79], p=0.045). Gynecologic cancers in females (OR=3.77 [2.82-4.99], p<0.0001) and urogenital cancers in males (OR=1.56 [1.17-2.06], p=0.0018) were strong risk factors. Additional targeted therapy, particularly lenvatinib (OR=3.79 [2.71-5.15], p<0.0001) and cabozantinib (OR=2.69 [1.66-4.09], p<0.0001) significantly increased the risk (OR=1.87 [1.52-2.29], p<0.0001) and this risk appeared to be more pronounced in females (OR=2.32 [1.76-3.02], p<0.0001). Additional chemotherapy was associated with a significantly reduced risk in males (OR=0.65 [0.42-0.96], p=0.042). However, doxorubicin (OR=2.58 [1.10-5.05], p=0.013) and cyclophosphamide (OR=2.36 [0.93-4.83], p=0.038) were linked to an elevated risk. Conclusions: Our findings demonstrated that ICIs could lead to a wide range of irRAEs in both males and females. Additional therapies could change the risk of irRAEs. Despite the current lack of high-quality clinical data on this topic, it is reasonable to inform patients about the plausible risk of irRAEs.