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.

Thoracic cancers international COVID-19 collaboration (TERAVOLT): Small-cell lung cancer andother rare thoracic malignancies

Background: At the last update of the TERAVOLT registry, patients with thoracic malignancies and COVID-19showed a high mortality rate (35.5% overall and 31% due to COVID-19) compared to the general population and toother solid tumors. Major determinants of mortality were age, Eastern Cooperative Oncology Group PerformanceStatus (ECOG-PS), and previous administration of chemotherapy. No cancer-specific data are available with respectto small-cell lung cancer (SCLC) and other rare thoracic malignancies. Methods: TERAVOLT is an international, multicenter observational registry launched to collect data on patients withthoracic malignancies diagnosed with COVID-19 infection. Risk factors for hospitalization and mortality wereidentified by Wilcoxon rank sum tests (continuous variables) or χ2 tests (categorical variables). Here we present thesubgroup analyses of SCLC and other rare thoracic malignancies, including malignant pleural mesothelioma (MPM), thymic carcinoma/thymoma, and carcinoid/neuroendocrine lung tumors. Results: As of June 4th, 2020, a total of 581 patients with COVID-19 and thoracic cancers have been entered;among them, 66 (11%) were SCLC, 22 (4%) were MPM, 18 (3%) were thymic carcinoma/thymoma, 12 (2%) werecarcinoid/neuroendocrine lung tumors, and 442 (76%) NSCLC;21 were an unknown type. Among SCLC patients,54% were > 65 years old, 56% were males, 98% were current/former smokers, 31% had an ECOG-PS ≥ 2, 67%had stage IV disease, 82% were on current oncologic treatment at the COVID-19 diagnosis, and 58% werereceiving chemotherapy alone or in combination with immune checkpoint inhibitors. Among other non-NSCLCpatients, 56% were > 65 years old, 56% were males, 69% were current/former smokers, 24% had an ECOG-PS ≥ 2,50% had stage IV disease, 52% were on current oncologic treatment at the COVID-19 diagnosis, and 37% werereceiving chemotherapy alone or in combination with immune checkpoint inhibitors. Overall, 79.7% of the patientsrequired hospitalization, 15.4% were admitted to an ICU, and 39.8% died (36.2% due to COVID-19). Among SCLCpatients, 74.2% required hospitalization, 14.3% were admitted to an ICU, and 42.2% died (37.5% due to COVID-19).Among SCLC patients, age > 65 years old (p=0.81), gender (p=0.71), smoking status (p=1.0), ECOG-PS ≥2(p=0.17), disease stage of IV (p=0.37), and having received chemotherapy alone or with checkpoint inhibitors(p=0.84) were not associated with mortality. Conclusions: This analysis confirmed that patients with thoracic malignancies have a high mortality and risk forhospitalization due to COVID-19 overall. SCLC patients showed the highest mortality rate among thoracic cancerpatients.

Thoracic Cancers International COVID-19 Collaboration (TERAVOLT): Impact of type of cancer therapy and COVID therapy on survival

Background: Early reports on cancer patients infected with COVID-19 have suggested a high mortality rate compared to the general population. Patients with thoracic malignancies are considered high risk given their age, preexisting comorbidities, smoking, and pre-existing lung damage in addition to therapies administered to treat their illness. Method: We launched a global consortium to collect data on patients with thoracic malignancies diagnosed with COVID-19 infection to understand the impact on this patient population. Goals of this consortium are to provide data for guidance to oncology professionals on treating patients with thoracic malignancies while understanding the risk factors for morbidity and mortality from this novel virus. Results: As of April 23, 2020, a total of 295 patients across 59 centers and 9 countries have been entered;median age 68, 31% female, 79% current/former smokers, HTN and COPD most common comorbidities;73% NSCLC, 14% SCLC, 4% meso and thymic, 49% patients with stage IV disease, majority on chemo or chemo-IO and 24% receiving RT. The use of IO or chemo-IO does not appear to impact risk of hospitalization, while treatment with TKI appears to be associated with a decreased risk of hospitalization. 73% patients required hospitalization, most common therapy given to treat COVID was antibiotics 67%, antivirals 33%, and steroids 30%. Conclusion: With an ongoing global pandemic of COVID-19 our data suggest that patients with thoracic malignancies are at high risk for hospitalization. Updated results to be presented will include impact on specific chemo-IO regimens and number of lines of therapy, which may impact hospitalization and risk of death as well as which therapies administered may impact survival in patients treated for COVID-19.

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.