Association of SARS-CoV-2 vaccination with survival outcomes in patients with metastatic solid tumors treated with immune checkpoint inhibitors.

2591 Background: Patients with cancer experience disproportionately high morbidity and mortality from SARS-CoV-2 infection, and COVID-19 vaccination is recommended for all patients with cancer. Although vaccines primarily reduce infection related complications, emerging data suggest SARS-CoV-2 mRNA vaccines may also enhance antitumor immune responses and potentially synergize with immune checkpoint inhibitors (ICIs). We evaluated survival outcomes in vaccinated versus unvaccinated patients with metastatic solid tumors treated with immunotherapy. Methods: Data for adults with metastatic cancers for which ICIs are indicated were obtained from the TriNetX Research Network (2019–2024). Patients were classified by receipt of ≥1 SARS-CoV-2 mRNA vaccine around the time of ICI initiation (±1 year) and compared with unvaccinated patients. Those with prior systemic antineoplastic, endocrine, or immunosuppressive therapy before ICI initiation or who developed COVID-19 were excluded. Cohorts were propensity matched for demographics, cancer type, comorbidities, and laboratory values. Outcomes included overall survival at 90 days, 1 year, and 5 years using Kaplan–Meier analyses, and all-cause hospitalization and immune-related adverse events (irAEs) within 90 days. Results: After matching, 543 vaccinated and 543 unvaccinated patients were well balanced. Vaccination was not associated with increased irAEs, with similar rates of any irAE (19.0% vs 17.9%, p=0.64), gastrointestinal (3.87% vs 3.87%, p=1.00), dermatologic (11.8% vs 10.7%, p=0.56), and neurologic events (2.76% vs 2.39%, p=0.70); pulmonary and hepatic irAEs were rare. Hospitalization rates were comparable (24.9% vs 23.9%, p=0.72). Vaccinated patients demonstrated improved intermediate-term survival, with higher 1-year survival (73.35% vs 64.12%; HR 0.70, 95% CI 0.56–0.87, p=0.001), with trends toward benefit at 90 days (HR 0.69, p=0.053) and 5 years (HR 0.85, p=0.066). Landmark analysis from 1 to 5 years showed no significant survival difference (HR 1.15, p=0.34). Consistent 1-year survival benefits were observed in lung cancer (65.93% vs 52.56%; HR 0.63, p=0.0005) and melanoma (80.25% vs 68.65%; HR 0.56, p=0.0355). Conclusions: In this large propensity-matched real-world cohort of metastatic solid tumor patients receiving immune checkpoint inhibitors, COVID-19 vaccination was not associated with increased immune-related toxicity or hospitalization and was associated with significantly improved 1-year overall survival. Attenuation of the survival association in landmark analyses suggests potential time-related bias, supporting the need for further studies with precise exposure timing.