995MO - Association of SARS-COV-2 mRNA vaccines with tumor PD-L1 expression and clinical responses to immune checkpoint blockade

Background

We previously found that mRNA vaccines encoding irrelevant antigens enhance responses to immune checkpoint inhibition (ICI) in murine models by increasing PD-L1 expression in tumors. We hypothesized that mRNA vaccines targeting SARS-COV-2 would similarly sensitize tumors to ICI by stimulating PD-L1 expression.

Methods

We utilized institutional databases to identify patients with Stage III/IV non-small cell lung cancer (NSCLC) (n=2406) or metastatic melanoma (n=757) with biopsy specimens between August 2019 and August 2023, as well as a separate “tissue agnostic” cohort with pathology reports that included the term “PD-L1” from August 2020 to November 2023 (n=5,524). Clinical, pathological, and molecular data, along with SARS-COV-2 vaccination dates (if applicable), were extracted for each patient. Differences between groups were assessed with Wilcoxon rank-sum tests. Survival was evaluated with Gehan-Breslow-Wilcoxon tests.

Results

Receipt of a SARS-COV-2 mRNA vaccine within 100 days prior to biopsy was associated with a 23% increase in mean tumor proportion score (TPS) of PD-L1 (31% vs 26%, p=0.029) and a 28% increase in the frequency of TPS > 50% (36% vs 28%, p=0.049) among patients with NSCLC, and a 55% increase in mean TPS (14% vs 8.9%, p=0.029) in the tissue agnostic cohort. Among NSCLC patients who were treated with ICI, receipt of a SARS-COV-2 mRNA vaccine within 100 days of ICI initiation was associated with a doubling of median OS (558 days vs 1120 days) and three-year overall survival (OS) (30.7% vs 57.2%, HR 0.57, 95% CI 0.44-0.74, p<0.001). In contrast, SARS-COV-2 mRNA vaccination had no impact on OS among NSCLC patients who were not treated with ICI. In the melanoma cohort, receipt of a SARS-COV-2 mRNA vaccine within 100 days of ICI initiation was associated with substantially improved OS (HR 0.42, 95% CI 0.24-0.74, p=0.003), distant metastasis-free survival (HR 0.66, 95% CI 0.42-1.05, p=0.023), and progression free survival (HR 0.64, 95% CI 0.44-0.92, p=0.022).

Conclusions

SARS-COV-2 mRNA vaccines are associated with increases in PD-L1 expression across a wide range of histologies and improved survival in patients with metastatic melanoma and NSCLC treated with ICI.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Research reported in this publication was supported by generous philanthropic contributions to The University of Texas MD Anderson Lung Moon Shot Program, the National Cancer Institute under award numbers T32-CA196561-08 and P50CA221703, and the MD Anderson Cancer Center Support Grant P30 CA016672.

Disclosure

J.V. Heymach: Financial Interests, Personal, Advisory Board: Genentech, Mirati Therapeutics, Eli Lilly & Co., Janssen Pharmaceuticals, Boehringer Ingelheim Pharmaceuticals, Regeneron, Takeda Pharmaceuticals, BerGenBio, Jazz Pharmaceuticals, Curio Science, Novartis, AstraZeneca, BioAlta, Sanofi, Spectrum Pharmaceuticals, GSK, Spectrum; Financial Interests, Personal, Full or part-time Employment: MD Anderson Cancer Center; Financial Interests, Institutional, Other, International PI for clinical trials: AstraZeneca; Financial Interests, Institutional, Other, International PI for two clinical trials: Boehringer Ingelheim; Financial Interests, Personal and Institutional, Other, Developed a drug: Spectrum; Financial Interests, Institutional, Coordinating PI: Takeda. S.H.H. Lin: Financial Interests, Personal, Other, Consultant: XRAD Therapeutics; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Invited Speaker: Varian Medical Systems; Financial Interests, Personal, Full or part-time Employment: The University of Texas MD Anderson Cancer Center; Financial Interests, Personal, Ownership Interest, Co-Founder and Scientific Advisor: Seek Diagnostics; Financial Interests, Personal, Research Grant: STCube Pharmaceuticals, Beyond Spring Pharmaceuticals; Financial Interests, Personal, Funding: Nektar Therapeutics; Non-Financial Interests, Leadership Role, Co-Chair RTDT Committee: NRG Oncology. All other authors have declared no conflicts of interest.