ABSTRACT
Patients with cancer frequently receive immune-checkpoint inhibitors (ICIs), which may modulate immune responses to COVID-19 vaccines. Recently, cytokine release syndrome (CRS) was observed in a patient with cancer who received BTN162b2 vaccination under ICI treatment. Here, we analyzed adverse events and serum cytokines in patients with 23 different tumors undergoing (n = 64) or not undergoing (n = 26) COVID-19 vaccination under ICI therapy in a prospectively planned German single-center cohort study (n = 220). We did not observe clinically relevant CRS (≥grade 2) after vaccination (95% CI 0-5.6%; Common Terminology of Adverse Events v.5.0) in this small cohort. Within 4 weeks after vaccination, serious adverse events occurred in eight patients (12.5% 95% CI 5.6-23%): six patients were hospitalized due to events common under cancer therapy including immune related adverse events and two patients died due to conditions present before vaccination. Despite absence of CRS symptoms, a set of pairwise-correlated CRS-associated cytokines, including CXCL8 and interleukin-6 was >1.5-fold upregulated in 40% (95% CI 23.9-57.9%) of patients after vaccination. Hence, elevated cytokine levels are common and not sufficient to establish CRS diagnosis.
Subject(s)
COVID-19 Vaccines , COVID-19 , Neoplasms , COVID-19 Vaccines/adverse effects , Cohort Studies , Cytokine Release Syndrome , Cytokines , Humans , Immune Checkpoint Inhibitors , Immunotherapy/adverse effects , Interleukin-6 , Neoplasms/drug therapy , VaccinationABSTRACT
To date, few data are available regarding Adverse events (AEs) in cancer patients who are vaccinated for coronavirus disease 2019 (COVID-19) while being actively treated with Immune-checkpoint inhibitors (ICIs). We aimed to assess the safety of COVID-19 vaccines approved in Germany. Specifically, we investigated the frequency of general side effects and immune-related AEs of COVID-19 vaccination. A triage survey was used to collect the following information for patients with metastatic skin cancer: vaccine type, date of receipt of each dose of vaccine, and self-reported side effects. Clinical data were retrieved from the patients' medical records. Of 130 patients with metastatic skin cancer, 89 patients were on immunotherapy and received COVID-19 vaccination. Of these 89 patients (median age: 64 years; 57 [64%] men), 89% had melanoma, and 71% received ICI therapy with a PD-1 antibody. Eighty-eight percent received an mRNA-based COVID-19 vaccination. The median follow-up time was 125 days after the first vaccination, and 84 days after the second. The most common observed side effects were mild to moderate pain at the injection site (40%), followed by fatigue (24%). Grade 3 irAEs were reported in eight patients, seven of whom were on nivolumab plus ipilimumab combination treatment. Of the 19 patients vaccinated within 72 h before/after ICI, five developed irAEs within 17 days (1-17 days). This small cohort study suggests that approved COVID-19 vaccinations are safe for use in cancer patients receiving ICIs. However, some precautions should be taken, especially regarding the timing of vaccination and ICI treatment.