LBA8 Vaccination against SARS-CoV-2 in patients receiving chemotherapy, immunotherapy, or chemo-immunotherapy for solid tumors

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.

Dutch oncology COVID-19 Consortium (DOCC): Outcome of COVID-19 in patients with cancer in a nationwide cohort study

Background: The coronavirus disease 2019 (COVID-19) pandemic is having significant impact on oncological care (Joode et al, Eur J Cancer 2020;136:132-139) and patients with cancer might have an increased risk for severe outcome of COVID-19. In order to identify risk factors associated with a worse outcome of COVID-19, a nationwide registry was developed for patients with cancer and COVID-19. Methods: This ongoing multicentre nationwide observational cohort study was designed as a quality of care registry and is executed by the Dutch Oncology COVID-19 Consortium (DOCC), a collaboration of oncology physicians in the Netherlands. A questionnaire was developed to collect pseudonymised patient data on patients’ characteristics, cancer diagnosis, cancer treatment, and outcome of COVID-19. All patients with COVID-19 and a cancer diagnosis or cancer treatment in the past 5 years were eligible for inclusion. Results: To date, > 600 cancer patients diagnosed with COVID-19 have been registered by 45 Dutch hospitals. Data of 442 registered patients with at least 4 weeks follow-up were cleaned and 351 patients could be included for the first analyses. The main cancer diagnoses were non-small cell lung cancer (13.4%), breast cancer (13.4%), and chronic lymphocytic leukaemia (8.8%). Overall, 114 (32.3%) out of 351 patients with cancer died from COVID-19. In multivariate analyses, age ≥ 65 years (p < 0.001), male gender (p = 0.035), prior or other malignancy (p = 0.045), and active diagnosis of haematological malignancy (p = 0.046) or lung cancer (p = 0.003) were independent risk factors for a fatal outcome of COVID-19. In a subgroup analysis of patients with active malignancy, the risk for a fatal outcome was mainly determined by tumour type (haematological malignancy or lung cancer) and age (≥ 65 years). Conclusions: The findings in this registry indicate that patients with a haematological malignancy or lung cancer have an increased risk of a worse outcome of COVID-19. During the ongoing COVID-19 pandemic, these vulnerable patients should avoid exposure to SARS-CoV-2, whereas treatment adjustments and prioritizing vaccination, when available, should also be considered. Legal entity responsible for the study: Erasmus Medical Center. Funding: Dutch Cancer Society. Disclosure: D.W. Dumoulin: Honoraria (self), Speakers fee: MSD;Honoraria (self), Speakers fee : Roche;Honoraria (self), Speakers fee: Astazeneca;Honoraria (self), Speakers fee: BMS;Honoraria (self), Speakers fee: Novartis;Honoraria (self), Speakers fee: Pfizer. H.M. Westgeest: Honoraria (self): Astellas;Honoraria (self): Roche;Travel/Accommodation/Expenses: Ipsen. L.E.L. Hendriks: Advisory/Consultancy, Mentorship program with key opinion leaders: funded by AstraZeneca: AstraZeneca;Honoraria (self), Educational webinars: Quadia;Research grant/Funding (institution): AstraZeneca;Advisory/Consultancy, Paid to institution: Eli Lilly;Advisory/Consultancy, Paid to institution: Roche Genentech;Advisory/Consultancy, Paid to institution: Pfizer;Advisory/Consultancy, Advisory board and speakers fee all paid to institution: MSD;Advisory/Consultancy, Paid to institution: Takeda;Leadership role, Local PI of pharma initiated research: AstraZeneca;Leadership role, Local PI of pharma initiated research: Novartis;Leadership role, Local PI of pharma initiated research: BMS;Leadership role, Local PI of pharma initiated research: MSD / Merck;Leadership role, Local PI of pharma initiated research: GSK;Leadership role, Local PI of pharma initiated research: Takeda;Leadership role, Local PI of pharma initiated research: Blueprint Medicines;Leadership role, Local PI of pharma initiated research: Roche Genentech;Advisory/Consultancy, Paid to institution: Amgen;Advisory/Consultancy, Paid to institution: Boehringer Ingelheim;Advisory/Consultancy, Paid to institution: BMS;Advisory/Consultancy, Travel/Accommodation/Expenses, Advisory board paid to institution: Roche Genentech;Travel/Accommodation/Expenses: BMS;Research grant/Funding (institution): Roche Genentech;R search grant/Funding (institution): Boehringer Ingelheim. A-M.C. Dingemans: Honoraria (self): Roche;Honoraria (self): Eli Lilly;Honoraria (self): Boehringer Ingelheim;Honoraria (self): Pfizer;Honoraria (self): BMS;Honoraria (self): Novartis;Honoraria (self): Takeda;Honoraria (self): PharmaMar;Advisory/Consultancy, non financial support: AbbVie;Research grant/Funding (institution): BMS;Research grant/Funding (institution): Amgen. A.A.M. Van der Veldt: Honoraria (institution), Advisory/Consultancy: BMS;Honoraria (institution), Advisory/Consultancy: MSD;Honoraria (institution), Advisory/Consultancy: Pfizer;Honoraria (institution), Advisory/Consultancy: Sanofi;Honoraria (institution), Advisory/Consultancy: Eisai;Honoraria (institution), Advisory/Consultancy: Ipsen;Honoraria (institution), Advisory/Consultancy: Roche;Honoraria (institution), Advisory/Consultancy: Novartis;Honoraria (institution), Advisory/Consultancy: Merck;Honoraria (institution), Advisory/Consultancy: Pierre Fabre. All other authors have declared no conflicts of interest.