RESEARCH QUESTION In patients with cancer, the disease and immunotherapy and chemotherapy may significantly impact the ability to develop an effective immune-response to COVID-19 vaccination and could even increase the risk of adverse events.
OBJECTIVE To assess immune-response and adverse events after vaccination with one vaccine against COVID-19 in patients with cancer treated with immunotherapy and/or chemotherapy.
STUDY DESIGN This is a prospective multicenter, multicohort study.
STUDY POPULATION 4 cohorts:
A. Individuals without cancer (partners of patients in cohort B, C & D)
Patients with cancer treated:
B. with immunotherapy
C. with chemotherapy
Main inclusion criteria:
• > 17 years of age
• life expectancy > 12 months
• ability to provide informed consent
• last immunotherapy cycle <3 months of vaccination (cohort B & D)
• last chemotherapy cycle <4 weeks of vaccination (cohort C & D)
Main exclusion criteria:
• confirmed SARS-CoV-2 infection (current or previous)
• women who are pregnant or breastfeeding
• active hematologic malignancy
• immune-deficiency not related to cancer or cancer treatment
• systemic immune suppressive medication, including chronic steroid use >10 mg prednisone or equivalent
INTERVENTION Participants receive 2 vaccinations against COVID-19 according to the manufacturer’s instructions. Blood samples are collected before vaccination and at day 28 and 6 and 12 months after second vaccination. To evaluate vaccination related adverse events (AEs), patients will be asked to report local and systemic AEs for 7 days after each vaccination using a questionnaire. Similarly serious AEs (SAEs). Most patients receiving systemic cancer treatment experience multiple AEs, treatment or disease related. Vaccination related AEs are mainly expected within the first week after vaccination. Therefore, all immune related AEs = grade 3 are collected in cohorts B & D up to 28 days after last vaccination. Furthermore, AEs of special interest (AESIs) will be collected for the study duration in cohorts B-D.
Information on incidence of SARS-CoV-2 infection, outcome of COVID-19 during 12 months after vaccination is collected with questionnaires. For those who give separate consent, information on positive corona tests will also be collected from the RIVM.
ENDPOINTS The primary endpoint is the antibody-based immune-response on day 28 after the second vaccination. Participants will be classified as responders or non-responders. The definition of response will be based on a serological correlate of protection for COVID-19 based on SARS-CoV-2 spike (S)- protein-specific serum IgG antibody levels if established, and if not established, we will use seroconversion (= 4-fold increase of geometric mean concentration of anti-S protein IgG antibodies over baseline). This definition will be added before data analysis to ClinicalTrials.gov. The percentage of responders of each patient cohort will be compared with the percentage responders in the control group. Safety is a secondary endpoint is reported as percentage of solicited local and systemic AEs. Other secondary endpoints include longevity at 6 months and SARS-CoV-2 specific T cell response levels.
SAMPLE SIZE/DATA-ANALYSIS The primary endpoint is the antibody-based immune response day 28 after the second vaccination in patients receiving cancer treatment as compared to individuals without cancer. Participants are classified as responders or non-responders to vaccination against COVID-19. In patients treated with immunotherapy, we assume that the immune response rate is similar to that in individuals without cancer. In patients treated with chemotherapy or chemo-immunotherapy, we expect a lower immune response rate. As the percentage of responders is still unknown for vaccination against COVID-19, especially when a lower immune response rate is expected, a power calculation for different scenarios has been performed, thereby comparing cohorts B, C, and D separately with cohort A.
In summary, these power calculations indicate that for the c