ABSTRACT
Introduction: COVID-19 vaccination substantially reduces morbidity and mortality associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and severe illness. However, despite effective COVID-19 vaccines many questions remain about the efficacy of vaccines and the durability and robustness of immune responses, especially in immunocompromised persons. The NCI-funded Serological Sciences Network (SeroNet) is a coordinated effort including 11 sites to advance research on the immune response to SARS-CoV-2 infection and COVID-19 vaccination among diverse and vulnerable populations. The goals of the Pooling Project are: (1) to conduct real-world data (RWD) analyses using electronic medical records (EMR) data from four health care systems (Kaiser Permanente Northern California, Northwell Health, Veterans Affairs-Case Western, and Cedars-Sinai) to determine vaccine effectiveness in (a) cancer patients;(b) autoimmune diseases and (c) solid organ transplant recipients (SOTR);(2) to conduct meta-analyses of prospective cohort studies from eight SeroNet institutions (Cedars-Sinai, Johns Hopkins, Northwell Health, Emory University, University of Minnesota, Mount Sinai, Yale University) to determine post-vaccine immune responses in (a) lung cancer patients;(b) hematologic cancers/hematopoietic stem cell transplant (HSCT) recipients;(c) SOTR;(d) lupus. Method(s): For our RWD analyses, data is extracted from EMR using standardized algorithms using ICD-10 codes to identify immunocompromised persons (hematologic and solid organ malignancy;SOTR;autoimmune disease, including inflammatory bowel disease, rheumatoid arthritis, and SLE). We use common case definitions to extract data on demographic, laboratory values, clinical co morbidity, COVID-19 vaccination, SARS-CoV-2 infection and severe COVID-19, and diseasespecific variables. In addition, we pool individual-level data from prospective cohorts enrolling patients with cancer and other immunosuppressed conditions from across network. Surveys and biospecimens from serology and immune profiling are collected at pre-specified timepoints across longitudinal cohorts. Result(s): Currently, we have EMR data extracted from 4 health systems including >715,000 cancer patients, >9,500 SOTR and >180,000 with autoimmune conditions. Prospective cohorts across the network have longitudinal data on >450 patients with lung cancer, >1,200 patients with hematologic malignancies, >400 SOTR and >400 patients with lupus. We will report results examining vaccine effectiveness for prevention of SARS-CoV-2 infection, severe COVID-19 and post-acute sequelae of COVID-19 (PAS-C or long COVID) in cancer patients compared to other immunocompromised conditions. Conclusion(s): Our goal is to inform public health guidelines on COVID-19 vaccine and boosters to reduce SARS-CoV-2 infection and severe illness in immunocompromised populations.
ABSTRACT
COVID-19 presents a unique threat to patients with lung cancer, with mortality rates as high as ∼32%. Given the convergence of these two deadly diseases, the lung cancer research and advocacy communities rapidly mobilized in early 2020 to create the COVID Lung Cancer Consortium (CLCC), a global assembly of leading experts in thoracic oncology, immunology, virology, vaccines and patient advocacy. With ongoing robust exchange of data and shared learning and rational planning for clinical and laboratory investigations, the CLCC is bringing its collective expertise to bear on beginning to address the question of why patients with lung cancer are at such elevated risk of worse outcomes from COVID-19. These efforts led to a recently funded U54 CA260560 grant as part of the National Cancer Institute's SeroNet initiative to study the magnitude, quality and duration of antibody responses to SARS-CoV-2 infection in patients with lung cancer compared to healthy controls. In the first project, our Mt. Sinai U54 Serological Center of Excellence will follow a prospective lung cancer cohort (750 patients) and a matched non-lung cancer control group (750 individuals) to determine if there are differences in antibody responses related to age, gender, tobacco history, and race/ethnicity. Given that effective SARS-CoV-2 vaccines are now being deployed, the study will also analyze antibody responses to vaccination across these two patient cohorts. The second project will examine biological determinants correlating with susceptibility to infection, including analysis of both ACE2 and TMPRSS2 levels, and antibody-mediated neutralization in pre-clinical models of established lung cancer and normal lung epithelial cell lines. In order to capture a diverse and inclusive patient population, this effort will be supported by GO2 Foundation for Lung Cancer through its national network of Centers of Excellence. This rapid global mobilization of the lung cancer community through the CLCC and the resulting Serological Center of Excellence is positioned to answer fundamental questions regarding the susceptibility of patients with lung cancer to SARS-CoV-2 infection and severe COVID-19 disease and provide information to allow assessment of the value of vaccination and the utility of specifically designed vaccine programs for this high-risk patient population.
ABSTRACT
Background: Patients with thoracic malignancies may have increased risk for COVID-19 mortality. This risk may be attributable to age, comorbidities, smoking history, pulmonary disease burden and cancer-directed therapies. Methods: TERAVOLT is a global consortium examining outcomes and assessing risk factors associated with mortality of patients with thoracic malignancies and COVID-19 infection. Results: As of July 15, 2020, 1012 patients from 20 countries have been entered;median age was 68 with 58 % male, 80% current/former smokers, most common comorbidities of HTN (49%) & COPD (26%);82% NSCLC, 68 % patients with stage IV disease at COVID diagnosis, 65% on treatment (38% chemotherapy, 26% immune checkpoint inhibitor (ICI), 16 % targeted tyrosine kinase inhibitor (TKI). Of these, 72% were hospitalized;56% of patients developed complications, most frequently pneumonia (40%) and 47% who did not have prior oxygen therapy required it. 32% of patients died during their COVID-19 infection. Only 33 % of patients continued their oncology treatment after infection. Patients presenting with pneumonia (OR 2.7 2-3.5), consolidation (OR 2 CI 1,5-2,8), bilateral lung abnormalities (OR 2,8 CI 2-3,9) and pleural effusion (OR 2,7 CI 1,8-4) were at increased risk of mortality. In multivariate analysis age ≥ 65 (OR 1,53 CI 1,11-2,1), active smoking (OR 2 CI 1,3-3), higher stage of cancer (OR 1,9 CI 1,3-2,7), ECOG PS ≥2 (OR 3,7 CI 2,7-5), steroids prior to COVID diagnosis (OR 1,8 CI 1,2-2,7), were associated with increased risk of death, while chemotherapy and TKI therapy use were not and interestingly patients on immunotherapy appeared to be at decreased risk for mortality (OR 0,6 CI 0,5-0,97). Conclusions: Facing this ongoing global pandemic, TERAVOLT is the largest thoracic malignancy database confirming the high risk for COVID-19 mortality in this specific patient group. Physicians need to evaluate the risk of mortality from COVID-19 based on age, smoking status, stage of cancer, performance status, need for steroids and specific therapy in order to determine the appropriateness for cancer therapy and tailor patient care taking into account patients’ wishes and status of pandemic in the country. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: J. Baena Espinar: Advisory/Consultancy: AstraZeneca;Honoraria (self), Travel/Accommodation/Expenses: Angelini. F.R. Hirsch: Advisory/Consultancy: AstraZeneca;Advisory/Consultancy: BMS;Advisory/Consultancy: Merck;Advisory/Consultancy: Daiichi;Advisory/Consultancy: Genentech/Roche;Advisory/Consultancy: Lilly/Loxo;Advisory/Consultancy: Boehringer-Ingelheim. M. Tiseo: Honoraria (self), Speaker Bureau/Expert testimony, Research grant/Funding (institution): AstraZeneca;Advisory/Consultancy, Research grant/Funding (institution): Boehringer Ingelheim;Advisory/Consultancy: Novartis;Advisory/Consultancy: MSD;Advisory/Consultancy: BMS;Advisory/Consultancy: Takeda. E. Felip: Speaker Bureau/Expert testimony, Advisory role or Speaker's bureau: AbbVie;Speaker Bureau/Expert testimony, Advisory role or Speaker's bureau: AstraZeneca;Speaker Bureau/Expert testimony, Advisory role or Speaker's bureau: Blue Print Medicines;Advisory/Consultancy, Advisory role or speaker's bureau: Boehringer Ingelheim;Speaker Bureau/Expert testimony, Advisory role or Speaker's bureau: Bristol-Myers Squibb;Speaker Bureau/Expert testimony, Advisory role or Speaker's bureau: GSK;Advisory/Consultancy, Speaker Bureau/Expert testimony, Advisory role or Speaker's bureau: Eli Lilly;Advisory/Consultancy, Speaker Bureau/Expert testimony, Advisory role or Speaker's bureau: Guardant Health;Advisory/Consultancy, Speaker Bureau/Expert testimony, Advisory role or Speaker's bureau: Janssen;Advisory/Consultancy, Speaker Bureau/Expert testimony, Advisory role or Speaker's bureau: Medscape;Advisory/Consultancy, Speaker Bureau/Expert testimony, Advisory role or Speaker's bureau: Merck KGaA;Advisory/Consultancy, Speaker Bureau/Expert testimony, Advisory role or Spea er's bureau: Merck Sharp and Dohme;Advisory/Consultancy, Speaker Bureau/Expert testimony, Advisory role or Speaker's bureau: Novartis;Advisory/Consultancy, Speaker Bureau/Expert testimony, Advisory role or Speaker's bureau: Pfizer;Advisory/Consultancy, Speaker Bureau/Expert testimony, Advisory role or Speaker's bureau: prIME Oncology;Advisory/Consultancy, Speaker Bureau/Expert testimony, Advisory role or Speaker's bureau: Roche;Advisory/Consultancy, Speaker Bureau/Expert testimony, Advisory role or Speaker's bureau: Samsung;Advisory/Consultancy, Speaker Bureau/Expert testimony, Advisory role or Speaker's bureau: Springer;Advisory/Consultancy, Speaker Bureau/Expert testimony, Advisory role or Speaker's bureau: Takeda;Advisory/Consultancy, Advisory role or Speaker's bureau: Touchime;Research grant/Funding (self), Research Funding: Fundacion Merck Salud;Research grant/Funding (institution), Research Funding: Grant for Oncology Innovation;Full/Part-time employment, Board (Independent Member: Grifols Boards. H.A. Wakelee: Research grant/Funding (institution), Clinical Research grant: Gilead;Honoraria (self), Advisory/ Consultancy, advisor or consultant honoraria: AstraZeneca;Advisory/Consultancy, Research grant/Funding (institution), advisor or consultant, research: Xcovery;Advisory/Consultancy, advisor or consultant: Jassen;Advisory/Consultancy, advisor or consultant: Daiichi Sankyo, INC;Advisory/Consultancy, advisor or consultant: Helsinn;Advisory/Consultancy, advisor or consultant: Mirati;Advisory/Consultancy, advisor or consultant (not: Takeda;Advisory/Consultancy, advisor or consultant (not: Cellworks;Advisory/Consultancy, Research grant/Funding (institution), advisor or consultant (not: Genentech/Roche;Advisory/Consultancy, Research grant/Funding (institution), advisor or consultant (not: Merck;Travel/Accommodation/Expenses, CME presentation (travel funding): Clinical care options oncology, LLC;Travel/Accommodation/Expenses, CME presentation (travel funding): Fishawack facilitate LTD;Travel/Accommodation/Expenses, CME presentation (travel funding): Medscape;Travel/Accommodation/Expenses, CME presentation (travel funding): Onclive/intellisphere LLC;Travel/Accommodation/Expenses, CME presentation (travel funding): Philips Gillmore Oncology 2018;Travel/Accommodation/Expenses, CME presentation (travel funding): Physician education resource, LLC/MJH;Travel/Accommodation/Expenses, CME presentation (travel funding): Potomac center for medical education;Travel/Accommodation/Expenses, CME presentation (travel funding): Prime Oncology LLC (2018);Travel/Accommodation/Expenses, CME presentation (travel funding): Primo (2018);Travel/Accommodation/Expenses, CME presentation (travel funding): Research to practice;Travel/Accommodation/Expenses, CME presentation (travel funding): UpToDate;Travel/Accommodation/Expenses, CME presentation (travel funding): WebMdHealth;Honoraria (self), Research grant/Funding (institution), honoraria, research funding to: Novartis;Travel/Accommodation/Expenses, International professional society: RGCON- Rajiv gand conference;Travel/Accommodation/Expenses, International professional society: JLCS - japanese lung cancer society;Travel/Accommodation/Expenses, International professional society: KSMO - korean society of medical oncology;Full/Part-time employment, professor of medicine: Stanford university;Travel/Accommodation/Expenses, Scientific advisory committe - travel: ITMIG;Research grant/Funding (institution), research funding to institution: ACEA biosciences. M.C. Garassino: Honoraria (self): Boehringer Ingelheim;Honoraria (self), Local PI, Enrollment in clinical Trials in: Otsuka Pharma;Honoraria (self), Research grant/Funding (institution), PI, Enrollment and Steering: AstraZeneca;Honoraria (self), Research grant/Funding (institution), PI, Enrollment in clinical Trials in: Novartis;Honoraria (self), Research grant/Funding (institution), PI, Enrollment in clinical Trials in: BMS;Honoraria (self), Research grant/Funding (institution), PI, Enrollment in clinic l Trials in: Roche;Honoraria (self), Research grant/Funding (institution), PI, MISP in Thimic malignancies: Pfizer;Honoraria (self), Research grant/Funding (institution), PI, Enrollment in clinical Trials in: Celgene;Research grant/Funding (institution): Incyte;Research grant/Funding (institution): Inivata;Research grant/Funding (self): Takeda;Honoraria (self), PI, Enrollment in clinical Trials Thimic: Tiziana Sciences;Honoraria (self), PI, Enrollment in clinical Trials in: Clovis;Honoraria (self), PI, Enrollment in clinical Trials in: Merck Serono;Honoraria (self), Research grant/Funding (self), PI, Enrollment in clinical Trials in: Bayer;Honoraria (self), Research grant/Funding (institution), PI, Enrollment in clinical Trials in: MSD;Honoraria (self), Local PI, Enrollment and Steering: GlaxoSmithKline S.p.A.;Research grant/Funding (institution): Sanofi-Aventis;Honoraria (self), PI, Enrollment in clinical Trials: Spectrum Pharmaceutcials;Honoraria (self), PI, Enrollment in clinical Trials: Blueprint Medicine;Research grant/Funding (institution): Seattle Genetics;Research grant/Funding (institution): Daiichi Sankyo;Honoraria (self), PI, MISP in Thimic malignancies: Eli Lilly. S. Peters: Honoraria (self), Advisory/Consultancy, Advisory board + honorarium: AbbVie;Honoraria (self), Advisory/Consultancy, Advisory board + honorarium: Amgen;Honoraria (self), Advisory/Consultancy, Advisory board + honorarium: AstraZeneca;Honoraria (self), Advisory/Consultancy, Advisory board + honorarium: Bayer;Honoraria (self), Advisory/Consultancy, Advisory board + honorarium: Biocartis;Honoraria (self), Advisory/Consultancy, Advisory board + honorarium: Boehringer-Ingelheim;Honoraria (self), Advisory/Consultancy, Advisory board + honorarium: Bistrol-Myers Squibb;Honoraria (self), Advisory/Consultancy, Advisory board + honorarium:Clovis;Honoraria (self), Advisory/Consultancy, Advisory Board + honorarium: Daiichi Sankyo;Honoraria (self), Advisory/Consultancy, Advisory Board + honorarium: Debiopharm;Honoraria (self), Advisory/Consultancy, Advisory Board + honorarium: Eli Lilly;Honoraria (self), Advisory/Consultancy, Advisory Board + honorarium: F. Hoffmann-La Roche;Honoraria (self), Advisory/Consultancy, Advisory Board + honorarium: Foundation Medicine;Honoraria (self), Advisory/Consultancy, Advisory Board + honorarium: Illumina;Honoraria (self), Advisory/Consultancy, Advisory Board + honorarium: Janssen;Honoraria (self), Advisory/Consultancy, Advisory Board + honorarium: Merck Sharp and Dohme;Honoraria (self), Advisory/Consultancy, Advisory Board + honorarium: Merck Serono;Honoraria (self), Advisory/Consultancy, Advisory Board + honorarium: Merrimack;Honoraria (self), Advisory/Consultancy, Advisory Board + honorarium: Novartis;Honoraria (self), Advisory/Consultancy, Advisory Board + honorarium: Pharma Mar;Honoraria (self), Advisory/Consultancy, Advisory Board + honorarium: Pfizer;Honoraria (self), Advisory/Consultancy, Advisory Board + honorarium: Regeneron;Honoraria (self), Advisory/Consultancy, Advisory Board + honorarium: Sanofi;Honoraria (self), Advisory/Consultancy, Advisory Board + honorarium: Seattle Genetics and Takeda;Honoraria (self), Speaker Bureau/Expert testimony, Talk + honorarium: AstraZeneca;Honoraria (self), Speaker Bureau/Expert testimony, Talk + honorarium: Boehringer-Ingelheim;Honoraria (self), Speaker Bureau/Expert testimony, Talk + honorarium: Bristol-Myers Squibb;Honoraria (self), Speaker Bureau/Expert testimony, Talk + honorarium: Eli Lilly;Honoraria (self), Speaker Bureau/Expert testimony, Talk + honorarium: F. Hoffmann-La Roche;Honoraria (self), Speaker Bureau/Expert testimony, Talk + honorarium: Merck Sharp and Dohme. L. Horn: Advisory/Consultancy, Consulting: AstraZeneca;Advisory/Consultancy, Consulting: Genentech-Roche;Advisory/Consultancy, Consulting: Incyte;Advisory/Consultancy, Consulting: Merck;Advisory/Consultancy, Consulting: Pfizer;Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses, Consulting and travel to meeting: Xcovery;dvisory/Consultancy, Consulting: EMD Serono;Advisory/Consultancy, Consulting: Tesaro;Advisory/Consultancy, Consulting: AbbVie;Research grant/Funding (self): Boehringer Ingelheim;Research grant/Funding (self), Travel/Accommodation/Expenses, Honorarium: BMS;Honoraria (self), Honorarium: Medscape;Honoraria (self), Honorarium: PER;Honoraria (self), Honorarium: Research to Practice;Honoraria (self), Honorarium: OncLive;Advisory/Consultancy, Consulting: Amgen;Advisory/Consultancy, Consulting: Bayer. All other authors have declared no conflicts of interest.