Main Session
Sep
29
PQA 07 - Head and Neck Cancer, Lung Cancer/Thoracic Malignancies, and Nursing and Supportive Care
3447 - Systemic Immune Activation by mRNA Vaccination Synergizes with Immune Checkpoint Inhibition and Radiotherapy: A Single-Institution Analysis
Presenter(s)
Sage Copling, BS - MD Anderson Cancer Center, Houston, TX
S. A. Copling1, A. Grippin2, N. Li3, C. Braun4, R. Lin5, and S. H. Lin6; 1McGovern Medical School, Houston, TX, 2Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Gainesville, FL, 3The University of Texas MD Anderson Cancer Center, Houston, TX, 4Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 5Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, 6Department of Thoracic Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
Purpose/Objective(s):
We previously reported that mRNA vaccines induce systemic innate immune activation that sensitizes tumors to immune checkpoint inhibitors (ICIs). However, the interaction between mRNA vaccination and other therapies, including radiotherapy, remains unknown. Here, we utilized a large single-institution dataset evaluating the association between mRNA vaccine timing and survival using causal inference methods, and explored preclinical interactions between mRNA vaccination and radiotherapy.Materials/Methods:
We evaluated a large single-institutional retrospective cohort study of patients who started their first ICI between March 2021 and February 2023. Patients were stratified by the timing of mRNA vaccination relative to ICI initiation (within 30 days; within 100 days). Inverse probability weighting models were generated based on baseline covariates including age, performance status, histology, stage, concurrent therapy, demographics, previous therapies, and comorbidities. Cox proportional hazards regression assessing the relationship between recent vaccination and overall survival (OS) were run on weighted groups. We then utilized preclinical models of non-small cell lung cancer (NSCLC) (Lewis Lung Carcinoma) to evaluate the effects of mRNA vaccines and radiotherapy on tumor growth.Results:
Among 5,858 patients who started ICI in the study’s timeframe, OS was improved inpatients who received a COVID mRNA vaccine within 100 days before their first ICI (n = 998) relative to those who did not (n = 4,860) (HR 0.84, 95% CI 0.74-0.94). Interval compression revealed that OS was also improved for patients vaccinated with mRNA vaccines within 30 days before initiating ICIs (n = 371) (HR 0.64, 95% CI 0.52-0.78). Among a subset of patients with non-metastatic NSCLC in our dataset who received radiation in the 6 months before ICI start (n = 126), patients vaccinated with mRNA vaccines within 100 days before ICI start lived significantly longer (HR: 0.44, 95% CI 0.20-0.97). In preclinical models, LLC-bearing C57BL6 mice receiving radiation (RT), ICI and mRNA vaccination experienced statistically improved survival compared to any other group, including ICI + mRNA vaccination (p=0.0063) and ICI + RT ( p < 0.0001).Conclusion:
Clinical and preclinical data in this study support synergy between mRNA vaccination, ICI, and radiotherapy.