Impact of COVID-19 mRNA vaccines on survival outcomes in patients with solid tumors receiving immunotherapy: A large-scale retrospective study.

2637 Background: Immune checkpoint inhibitors (ICIs) became the cornerstone in the treatment of solid tumors. While personalized cancer vaccines have yet to overcome complex scalability and manufacturing challenges, preclinical data suggests SARS-CoV-2 mRNA vaccines prime innate immunity, potentially enhancing ICI efficacy. A study by Grippin et al. evaluated the use of mRNA vaccine in NSCLC and melanoma patients receiving ICI and showed improved median and three-year overall survival (OS). We conducted a multicenter retrospective study to determine if this survival benefit extends across a broader range of ICI-treated solid tumors. Methods: Using the TriNetX global network, we identified adults (≥18) with solid tumors (NSCLC, melanoma, colorectal, hepatobiliary, gallbladder, gastric, bladder, pancreatic, renal, breast, head and neck, and esophageal) who received ICI treatment. The experimental group received SARS-CoV-2 mRNA vaccine within 100 days of ICI initiation; controls received no mRNA vaccine from 100 days pre-index through follow-up. Exclusion criteria: COVID-19 infection within 100 days and through the follow-up period. 1:1 propensity score matching (PSM) balanced demographics and comorbidities. Primary endpoint was median OS, including tumor-specific subgroup analyses. Survival was assessed via Kaplan-Meier and log-rank tests. Results: After PSM, we had 15,374 matched patients (7,687 per group). Vaccination within 100 days of ICI was associated with improved median OS (1,421 vs 667 days; HR 0.63; 95% CI 0.60-0.66; p<.001). Benefit was observed in 10 of 12 tumor types. Strongest effects were in NSCLC (n=7,350; HR 0.64), melanoma (n=2,684; HR 0.61; landmark survival 62.1% vs 50.3%), hepatobiliary (n=1,428; HR 0.64), colorectal (n=1,068; HR 0.67), gastric (n=792; HR 0.68), bladder (n=1,398; HR 0.63), pancreatic (n=240; HR 0.65), renal (n=1,996; HR 0.64), head and neck (n=964; HR 0.68), and esophageal (n=828; HR 0.63). No significant benefit was seen in breast (n=1,412; HR 0.85) or gallbladder cancer (n=58; HR 0.88). Conclusions: SARS-CoV-2 mRNA vaccination within 100 days of ICI therapy was associated with improved survival across solid tumors. These results suggest off-the-shelf RNA therapeutics may be scalable, cost-effective enhancers of cancer immunotherapy. Prospective studies are needed to confirm these findings and define the impact of universal mRNA strategies.