ABSTRACT
Background: Patients with cancer have an increased risk of complications from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. Vaccination is recommended, but the impact of chemotherapy and immunotherapy on immunogenicity and safety is still unclear. Methods: This prospective multicenter non-inferiority trial comprises four cohorts: individuals without cancer (A) and patients with solid tumors who were treated with immunotherapy (B), chemotherapy (C) or chemo-immunotherapy (D). Participants received two mRNA-1273 vaccinations 28 days apart. The primary endpoint was SARS-CoV-2 Spike S1-specific IgG serum antibody response, defined as >10 binding antibody units (BAU)/ml 28 days after the second vaccination. We also assessed the virus neutralizing capacity of these antibodies, SARS-CoV-2 Spike-specific interferon-gamma T cell response, and adverse events. Results: Of the 791 participants enrolled, 743 were evaluable for the primary endpoint in cohort A (n=240), B (n=131), C (n=229) and D (n=143). A SARS-CoV-2-binding antibody response was found in 100%, 99.3%, 97.4%, and 100% of the participants in cohorts A, B, C, and D, respectively. To discriminate between suboptimal and adequate responders, we defined a cut-off level at 300 BAU/ml, based on neutralizing capacity. The antibody response was considered adequate after the first vaccination in 66.0%, 37.1%, 32.5%, and 33.3% of the participants in cohorts A, B, C, and D, respectively. This raised 28 days after the second vaccination to respectively 99.6%, 93.1%, 83.8%, and 88.8% in cohorts A, B, C, and D. Spike-specific T cell responses were detected in 46.7% of suboptimal and non-responders. No new safety signals were observed. Conclusions: mRNA-1273 vaccination is safe in the patient populations studied. For each cohort, the proportion of patients with a SARS-CoV-2-binding antibody response after two vaccinations is non-inferior compared to individuals without cancer. However, a significant minority lacks an adequate response. Most patients have an antibody concentration increase after the second vaccination. Therefore, an additional booster may turn inadequate into adequate responders. Clinical trial identification: NCT04715438. Legal entity responsible for the study: University Medical Center Groningen, the Netherlands. Funding: ZonMw, The Netherlands Organisation for Health Research and Development. Disclosure: All authors have declared no conflicts of interest.
ABSTRACT
Background: The COVID-19 pandemic COVID had a severe impact on medical care in The Netherlands. So far, few studies have investigated the influence of COVID-19 on advanced melanoma care nationwide. This study aims to investigate the impact of COVID-19 on the systemic treatment of unresectable stage III and IV advanced melanoma patients in the Netherlands. Methods: Data were obtained from the Dutch Melanoma Treatment Registry (DMTR), a population-based nationwide registry of all stage III and IV melanoma patients amenable for systemic treatment. We compared two patient groups dependent on the date of the first diagnosis of metastasis: during the first COVID-19 wave (March 15th 2020 until May 22nd 2020), and a control group during the same period one year earlier. Furthermore, we divided patients into three geographical regions within the Netherlands (north, middle and south). These regions were based on the maximum number of hospital admissions for COVID-19 patients during the first wave, using data from the National Intensive Care Evaluation (NICE). COVID-19 incidence was highest in the southern part of The Netherlands. We investigated baseline characteristics, type of systemic therapy, time from diagnosis of the irresectable stage III or IV melanoma until the start of systemic therapy, postponement of anti-PD-1 courses in patients actively being treated during the predefined time periods and progression-free survival (PFS) and overall survival (OS) using Kaplan-Meier estimates. Results: During the first COVID-19 wave, 104 patients were diagnosed with advanced melanoma versus 166 patients during the control period in 2019. No significant differences were found in patient and tumor characteristics, type of systemic therapies or in the time from diagnosis until the start of systemic therapy, between the different periods. However, during the first wave, the time between diagnosis until the start of treatment was significantly longer in the southern regions as compared to the northern and middle regions (33 vs 9 and 15 days, p-value < 0.05). Anti-PD-1 antibody treatment courses were postponed in 79 patients (15.5%) during the first wave versus four patients (1.1%) in the control period. Significantly more patients had a postponed course in the south during the first wave compared to the middle and northern regions (30.2% vs 2.7% vs 16.7%, p-value < 0.001). With limited follow-up, thus far no significant differences in PFS and OS were found. Conclusions: Advanced melanoma care in the Netherlands was severely affected by the COVID-19 pandemic. In the south, where COVID- 19 incidence was highest in the first wave, the start of systemic treatment for advanced melanoma was more often delayed, and treatment courses were more frequently postponed. Longer follow-up is needed to establish whether this has had an impact on patient outcome.