The impact of COVID-19 mRNA vaccines on immune-related adverse events in patients with cancer receiving immune checkpoint inhibitors.

person Mengni Guo Department of Oncology/Hematology, Loma Linda University Medical Center, Loma Linda, CA info_outline Mengni Guo, Zohaib Ahmed, Phuong Nguyen, Kashaf Zaidi, Raphael Itzkowitz, Esther G Chong, Dani Ran Castillo, Huynh Le Cao

Authors person Mengni Guo Department of Oncology/Hematology, Loma Linda University Medical Center, Loma Linda, CA info_outline Mengni Guo, Zohaib Ahmed, Phuong Nguyen, Kashaf Zaidi, Raphael Itzkowitz, Esther G Chong, Dani Ran Castillo, Huynh Le Cao Organizations Department of Oncology/Hematology, Loma Linda University Medical Center, Loma Linda, CA, Brigham and Women's Hospital, Boston, MA, AdventHealth Orlando, Orlando, FL, City of Hope, Duarte, CA Abstract Disclosures Research Funding No funding sources reported Background: Cancer patients are a vulnerable population to COVID-19. COVID-19 mRNA vaccines have shown to decrease hospitalization and death risk from COVID-19 in cancer patients. Concurrent COVID-19 vaccination and immune checkpoint inhibitors (ICIs) use may impact immune-related adverse events (irAEs) synergistically. Limited data exist on how COVID-19 mRNA vaccines affect irAEs in ICI-treated cancer patients, especially those with breakthrough infections. Methods: We retrospectively analyzed adult patients with malignant solid tumors receiving ICIs at a single cancer institute (January 2020 to July 2021). Fully vaccinated status is defined as two consecutive doses of mRNA vaccines (BNT162b2 and mRNA-1273). Patients who were partially vaccinated, fully vaccinated post COVID-19 infection, vaccinated with non-mRNA COVID-19 vaccines, or last visit within 30 days post vaccination were excluded. All COVID-19 infections were confirmed by PCR. In the vaccinated group, only post-vaccination irAEs were considered as events. Results: 443 patients were included in our study, with 251 (56.7%) vaccinated and 192 (43.3%) unvaccinated. The baseline characteristics were similar between the two groups, except for age (vaccinated median 68 years, unvaccinated median 62 years, p=0.004). With a median follow-up of 12 months, incidences of all-grade irAEs (19.1% vs. 20.3%, p=0.72) and severe irAEs (5.6% vs. 4.2%, p=0.66) were comparable between vaccinated and unvaccinated groups. 34 breakthrough COVID-19 infections occurred. In the vaccinated group, a non-significant trend of higher all-grade irAEs incidence was noted in the COVID-19 infected subgroup compared to uninfected subgroup (29.4% vs. 17.5%, p = 0.11). Univariate analysis linked COVID-19 vaccination (OR 1.54, 95% CI 1.01-2.35, p=0.04) and ipilimumab + nivolumab use (OR 5.57, 95% CI 1.79-17.35, p=0.003) to a higher risk of all-grade irAEs in the entire cohort. After multivariate adjustment, ipilimumab + nivolumab use remained the only variable associated with all-grade irAEs (OR 4.95, 95% CI 1.57-15.64, p=0.006). Conclusions: Our study suggests that COVID-19 mRNA vaccines do not increase irAE risk in cancer patients on ICIs. Fully vaccinated patients with breakthrough COVID-19 infections may safely continue ICI treatment without an increased irAE risk. IrAE Clinical features between vaccinated and unvaccinated groups. Variable Vaccinated Group n= 251 Unvaccinated Group n=192 P-value All-grade irAE, n (%) 48 (19.1) 39 (20.3) 0.72 Severe (grade 3 and above) irAE, n (%) 14 (5.6) 8 (4.2) 0.66 Corticosteroid use, n (%) 26 (10.4) 22 (11.5) 0.76 Additional immunosuppressant use, n (%) 3 (1.2) 1 (0.5) 0.63 Treatment interruption due to irAE, n (%) 30 (11.9) 28 (11.2) 0.48 Time to irAE, median (range) Treatment cycle 6 (1-52) 7 (1-72) 0.60 Days 161 (8-1505) 117 (7-1662) 0.68 Death-related to irAE, n (%) 1 (0.4) 0 (0.0) 1.00