Association of mRNA COVID-19 vaccination near immune checkpoint inhibitor initiation with outcomes: A real-world analysis.

2636 Background: Prior study showed mRNA COVID-19 vaccines can activate innate and adaptive immune pathways and have been hypothesized to “prime” anti-tumor immunity via increased tumor PD-L1 expression when administered near immune checkpoint inhibitor (ICI) initiation. We performed a real-world validation to evaluate the association between COVID-19 vaccination around ICI initiation and outcomes among patients with 4 advanced/metastatic solid tumors. Methods: Using ConcertAI Patient360 (US-based, de-identified, human-abstracted oncology EHR linked to medical/pharmacy claims and third-party mortality), we identified adults (≥18 years at diagnosis) with advanced/metastatic bladder cancer, melanoma, non-small cell lung cancer (NSCLC), or renal cell carcinoma (RCC) who initiated an ICI between Jan 2021 and Mar 2024. Exposure was receipt of ≥1 mRNA COVID-19 vaccine within 100 days of ICI initiation. Exposed patients were propensity score–matched 1:1 to unexposed patients on demographics (age, sex, race, ethnicity) and clinical factors (baseline steroid use, ICI initiation year, Charlson Comorbidity Index, ECOG performance status, BMI, and tumor type). Real-world OS (rwOS) and real-world PFS (rwPFS) were estimated by Kaplan-Meier; hazard ratios (HRs) were estimated using univariate Cox models (post-match) and multivariable Cox models (residual confounding sensitivity), overall and by tumor type. Results: Among 7085 eligible patients, 1,513 were vaccinated around ICI initiation. After matching, 3,018 patients (1,509 per group) had evaluable time-to-event data and were included in Kaplan-Meier and Cox analyses (tumor mix: NSCLC 73.6%, RCC 11.7%, bladder 8.5%, melanoma 6.3%). Overall, vaccination was associated with improved rwOS and rwPFS: median rwOS 19.52 vs 15.31 months (p<0.001) and median rwPFS 7.95 vs 6.37 months (p=0.002). Univariate Cox models favored vaccination for rwOS (HR 0.82; 95% CI 0.75–0.90; p<0.001) and rwPFS (HR 0.88; 95% CI 0.81–0.95; p=0.002), with consistent findings in multivariable models (rwOS HR 0.81; 95% CI 0.74–0.89; p<0.001; rwPFS HR 0.87; 95% CI 0.80–0.95; p=0.001). Twelve-month rwOS was 64.87% vs 54.45% (vaccinated vs unvaccinated). By tumor type, univariate (post-match) associations were directionally favorable and strongest in NSCLC (rwOS HR 0.79; 95% CI 0.71–0.87; p<0.001; rwPFS HR 0.85; 95% CI 0.77–0.93; p<0.001). Similar, non-significant trends were observed in smaller bladder and RCC cohorts; melanoma showed no association with rwOS. Conclusions: In this large propensity score–matched real-world cohort of ICI-treated patients, COVID-19 vaccination within 100 days of ICI initiation was associated with significant improvements in rwOS and rwPFS, particularly in NSCLC. Prospective validation and randomized clinical trials are warranted to confirm these findings.