Incidence and outcomes of rejection in solid organ transplant recipients treated with immune checkpoint inhibitors: A systematic review and meta-analysis.

Abstract

11068 Background: Immune checkpoint inhibitors (ICIs) are a cornerstone in the treatment of many solid tumors; however, their use in cancer patients with solid organ transplants (SOTs) poses unique challenges due to the risk of allograft rejection. We conducted a systematic review and meta-analysis of retrospective studies to determine the incidence of rejection and associated outcomes in SOT patients treated with ICIs. Methods: We searched PubMed, Embase, and Scopus to identify retrospective studies examining ICI therapy in SOT patients with cancer. Primary endpoints were the incidence of rejection and its clinical outcomes. Statistical analyses were performed using the "meta" package in R. Results: Seventeen studies encompassing 587 patients were included. The most frequent malignancies were hepatocellular carcinoma (HCC), melanoma, and cutaneous squamous cell carcinoma (cSCC). The overall rejection incidence was 16% (95% CI: 9%-24%), with variation across cancer types: multiple cancers (18%, 95% CI: 5%-36%), HCC (22%, 95% CI: 15%-29%), and cSCC (4%, 95% CI: 0%-21%). Rejection incidence was higher among liver transplant recipients (18%, 95% CI: 10%-26%) compared to kidney recipients (16%, 95% CI: 5%-32%). Geographic differences were observed, with rejection rates of 15% (95% CI: 1%-37%) in U.S.-based studies, 25% (95% CI: 18%-33%) in China, and 9% (95% CI: 0%-25%) in Korea. Pre-transplant ICI exposure was associated with a higher rejection rate (18%, 95% CI: 9%-28%) compared to post-transplant exposure (15%, 95% CI: 7%-26%). Outcomes of rejection varied, with 44% (95% CI: 24%-65%) achieving stabilization or resolution. Liver transplant recipients demonstrated higher resolution rates (67%, 95% CI: 46%-85%) compared to kidney recipients (27%, 95% CI: 7%-52%). Regional differences in resolution were notable, with higher rates reported in China (65%, 95% CI: 45%-83%) compared to the U.S. (26%, 95% CI: 13%-42%). Conclusions: This meta-analysis reveals a 16% overall rejection rate in SOT recipients treated with ICIs, higher in liver allografts and HCC, with regional disparities. Nearly half of patients who experienced rejection improved or stabilized, especially liver recipients. These findings underscore the need for personalized approaches to balance oncologic efficacy and graft survival in this complex population. Category Rate (% [95% CI]) Overall Rejection Rate 16 [9-24] Rejection by Cancer Type Multiple: 18 [5-36], HCC: 22 [15-29], cSCC: 4 [0-21] Rejection by Transplant Type Liver: 18 [10-26], Kidney: 16 [5-32] Rejection by Geography USA: 15 [1-37], China: 25 [18-33], Korea: 9 [0-25] Rejection by Timing Pre-Transplant: 18 [9-28], Post-Transplant: 15 [7-26] Overall Reversibility 44 [24-65] Reversibility by Transplant Type Liver: 67 [46-85], Kidney: 27 [7-52] Reversibility by Geography China: 65 [45-83], USA: 26 [13-42]