Outcomes of Solid Organ Transplant Recipients With Advanced Cancers Receiving Immune Checkpoint Inhibitors A Systematic Review and Individual Participant Data Meta-Analysis

IMPORTANCE Immune checkpoint inhibitors (ICIs) have improved overall survival in patients with advanced-stage cancers. However, data on their efficacy and safety in solid organ transplant recipients (SOTRs) are limited. OBJECTIVE To examine cancer-specific and patient survival among SOTRs with advanced-stage cancer receiving ICIs and identify factors associated with patient and graft outcomes. DATA SOURCES Electronic databases and clinical registries, including MEDLINE, Embase, ClinicalTrials.gov, Australia New Zealand clinical trials registry, and the World Health Organization International Clinical Trials Registry Platform, were searched from inception to June 2024 without language restriction. STUDY SELECTION Case reports and series, observational studies, and clinical trials that described the treatment of advanced-stage cancers using ICIs in SOTRs were included. DATA EXTRACTION AND SYNTHESIS Individual participant data were extracted and synthesized using a single-stage random-effect model. MAIN OUTCOMES AND MEASURES Time to cancer-related death was the primary outcome. The main secondary outcomes included time from ICI initiation to first rejection and cancer response according to Response Evaluation Criteria in Solid Tumors 1.1 criteria. Adjusted Cox proportional hazards regression models were conducted for time-to-event analyses. RESULTS Of 140 studies, 128 studies involving 343 SOTRs treated with ICI were included. Most participants were male (76.9%), kidney transplant recipients (70.9%), with a median (IQR) age of 63 years (14-88 years), and treated with programmed cell death protein-1 inhibitors (72.9%). Within 3 years of ICI initiation, 52.8% (95% CI, 43.9%-61.6%) died of cancers. Acute rejection occurred in 36.2% (95% CI, 30.7%-41.7%) at 1 year, and 18.4% (95% CI, 13.7%-23.1%) experienced graft loss at 1 year. Objective response at 1 year was 31.6% (95% CI, 25.0%-37.7%), with a higher response observed in patients with cutaneous squamous cell carcinoma (cSCC) (61.0% [95% CI, 45.5%-76.4%]) than melanoma (48.5% [95% CI, 26.8%-70.3%]), and other solid organ cancers (26.9% [95% CI, 14.5%-39.3%]). Transplant recipients with melanoma (hazard ratio [HR], 2.29; 95% CI, 1.31-3.99) and solid organ cancers (HR, 2.84; 95% CI, 1.70-4.74) experienced higher rates of cancer-related deaths than those with cSCC. Recipients with melanoma have a higher risk of acute rejection (HR, 2.88; 95% CI, 1.69-4.90) than cSCC. Maintenance with steroids and mammalian target of rapamycin inhibitors (mTORIs) was associated with a lower risk of rejection compared with other immunosuppressive agents (HR, 0.30; 95% CI, 0.14-0.63). CONCLUSIONS AND RELEVANCE In this study, cancer outcomes in SOTRs receiving ICIs varied by cancer type, with a higher probability of achieving response among those with cSCC than other cancers. Concurrent use of mTORIs and steroids during ICI therapy may reduce the risk of acute allograft rejection.