Safety and efficacy of immune checkpoint inhibitors in solid organ transplant recipients: A systematic review and individual patient data meta-analysis.

Abstract

2511 Background: Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment but pose unique challenges in solid organ transplant (SOT) recipients. Transplant rejection remains the predominant safety concern. We systematically evaluated the safety (focusing on allograft rejection) and efficacy of ICIs across all organ transplant types and ICI classes, providing updated evidence-based insights for clinical decision-making. Methods: A systematic review of PubMed, EMBASE, and SCOPUS databases was conducted in accordance with PRISMA guidelines. Studies reporting rejection or efficacy outcomes in SOT recipients treated with any class of ICI were included. The primary endpoints were the incidence of transplant rejection and survival following ICI therapy. Secondary endpoints included objective response rate (ORR) and progression-free survival (PFS) for malignancies. Analysis was performed using SPSS (V26.0) and R (V4.3.0). Results: Of 2682 screened abstracts, 198 studies involving 331 SOT recipients met inclusion criteria. The transplanted organs were liver (n=175), kidney (n=136), and heart (n=15). Rejection rates were highest in Kidney at 46.3% (63/136), followed by heart (40.0%, 6/15) and liver (26.9%, 47/175). Across ICI classes, rejection rates were: Anti-CTLA4 (25%) Anti-PD1 (40.6%) and Anti-PDL1 (0%). Rejection rates were lower in patients receiving ICI pre-transplant (25.9%) compared to post-transplant (40.9%). ORR varied by ICI class: Anti-CTLA4 (25%), Anti-PD1 (41.8%), Anti-PD1 + CTLA4 (28%), and Anti-PDL1 (72.7%). Cutaneous squamous cell carcinoma (cSCC) showed the highest ORR (49.1%), followed by hepatocellular carcinoma (40.8%) and melanoma (25.3%). Post-transplant rejection risk was lower with Anti-CTLA4 (OR 0.22), 3rd-line ICI therapy (OR 0.24), and corticosteroids (OR 0.46). Pre-transplant rejection risk decreased with >60-day washout periods (OR 0.10). Multivariate analysis identified key factors influencing rejection risk (Table 1). Conclusions: ICI therapy in SOT recipients is high-risk yet promising. Key strategies include prolonged washout periods, Anti-CTLA4 therapy, and late-line ICI use. Prospective studies are needed to refine protocols and identify predictive markers to improve outcomes in this population. Multivariate analysis results. Factor Total (OR) P-Value Pre-Transplant ICI administration (OR) P-Value Post-transplant ICI administration (OR) P-Value Age (<60 vs > 60) 0.79 0.42 0.85 0.82 0.62 0.18 Sex (M vs F) 1.12 0.75 1.36 0.7 1.23 0.63 CTLA-4 0.21 0.03 - - 0.22 0.04 Third line and later (vs 1st line) 0.26 0.01 0.17 0.44 0.24 0.01 NSCLC (vs HCC) 6.87 0.03 - - 3.59 0.23 RCC (vs HCC) 9.9 0.04 - - 5.88 0.11 Multiple tumors 19.18 0.01 - - 9.3 0.06 Washout period (<60 vs>=60) - - 0.1 <0.001 - -