key: cord-1052435-kvzadhp1
authors: Gomez, J.; Krammer, F.; Mack, P.; Rolfo, C.; Rohs, N.; Moore, A.; King, J.; Henschke, C.; Yankelevitz, D.; Shyr, Y.; Taioli, E.; Fontoura, B.; Brody, R.; Gerber, D.; Minna, J.; Bunn, P. A.; Garcia-Sastre, A.; Hirsch, F.
title: OA01.01 Analysis of Lung Cancer Patients Receiving SARS-CoV-2 Vaccines Revealed a Minority Subset With Poor Antibody Responses Relative to Controls
date: 2021-10-31
journal: Journal of Thoracic Oncology
DOI: 10.1016/j.jtho.2021.08.034
sha: 64e92700c0a424aa47c73de5321f6149ead30020
doc_id: 1052435
cord_uid: kvzadhp1

Introduction: Patients with lung cancer (LC) were reported to have a high case fatality rate (30-40%) from SARS-CoV-2 infection, raising the question of whether LC patients mount a weaker antibody response to natural infection and/or vaccination, compared to healthy controls (HCs). We previously analyzed antibody responses to SARS-CoV-2 mRNA vaccination in several hundred healthy individuals, stratified by previous SARS-CoV-2 infection status. Using a validated enzyme-linked immunosorbent assay (ELISA) to the full-length spike protein (PMC8183627, PMC7235504), we found strong responses to infection and a robust neutralizing antibody response to vaccination. We compare these results to data from individuals diagnosed with LC undergoing different types of cancer treatment. Methods: This is an ongoing, prospective, control-matched longitudinal cohort study of 750 LC patients in all stages with or without previous SARS-CoV-2 infection and/or vaccination, comparing SARS-CoV-2 antibody titers at baseline (time of enrollment) and at 3-, 6-, 12- and 24-month intervals. We examine the quality, magnitude, and duration of the SARS-CoV-2 antibody titers against the full-length spike protein compared to the matched (age, tobacco history, sex and ethnicity) HC cohort. Types of Analysis and Data Reporting: ELISAs are performed in a CLIA-certified laboratory using an FDA-approved antibody assay along with other well-established, research-grade assays. We hypothesized that LC patients have a weaker antibody response to SARS-Cov-2 infection and/or vaccination due to cancer or its treatment compared to matched HCs. The non-parametric Kruskal–Wallis test was used to test this hypothesis. If confirmed, a tailored vaccination program would be necessary to ensure immune protection in patient with LC. Results: 111 LC patients have been enrolled to date;with 78 receiving at least one vaccination and 33 unvaccinated. Median age is 69, with 58% female. 39 patients were fully vaccinated (defined as 14+ days after second vaccination). Partially vaccinated (after 1st vaccine dose) LC patients had a lower median antibody level than partially vaccinated HCs (p=0.01). Fully vaccinated LC patients had substantial antibody titers but a lower median antibody level than fully vaccinated HCs (p=0.01) with a subset not raising large antibody titers. Especially important were the 30% of partially vaccinated LC patients who did not develop neutralizing antibodies. To date, there were no significant differences in median antibody levels in LC patients by gender, smoking status, age (< or > 65 years old), or treatment (with or without chemotherapy, immune checkpoint inhibitors, or targeted therapy). Conclusion: While most (∼70%+) of LC patients mounted a good antibody response to vaccination, a subgroup had significantly lower anti-spike antibody/neutralizing levels compared to controls. Further studies are required to evaluate the role of further boost vaccinations in this patient population with a particular focus on patients not producing neutralizing antibodies to further understand the lack of response. We will continue to analyze the effect of systemic anti-cancer therapies as more data becomes available. Keywords: SARS-CoV-2, lung cancer, covid-19

Introduction: Patients with lung cancer (LC) were reported to have a high case fatality rate (30-40%) from SARS-CoV-2 infection, raising the question of whether LC patients mount a weaker antibody response to natural infection and/or vaccination, compared to healthy controls (HCs). We previously analyzed antibody responses to SARS-CoV-2 mRNA vaccination in several hundred healthy individuals, stratified by previous SARS-CoV-2 infection status. Using a validated enzyme-linked immunosorbent assay (ELISA) to the full-length spike protein (PMC8183627, PMC7235504), we found strong responses to infection and a robust neutralizing antibody response to vaccination. We compare these results to data from individuals diagnosed with LC undergoing different types of cancer treatment. Methods: This is an ongoing, prospective, control-matched longitudinal cohort study of 750 LC patients in all stages with or without previous SARS-CoV-2 infection and/or vaccination, comparing SARS-CoV-2 antibody titers at baseline (time of enrollment) and at 3-, 6-, 12-and 24-month intervals. We examine the quality, magnitude, and duration of the SARS-CoV-2 antibody titers against the full-length spike protein compared to the matched (age, tobacco history, sex and ethnicity) HC cohort. Types of Analysis and Data Reporting: ELISAs are performed in a CLIAcertified laboratory using an FDA-approved antibody assay along with other well-established, research-grade assays. We hypothesized that LC patients have a weaker antibody response to SARS-Cov-2 infection and/or vaccination due to cancer or its treatment compared to matched HCs. The non-parametric KruskaleWallis test was used to test this hypothesis. If confirmed, a tailored vaccination program would be necessary to ensure immune protection in patient with LC. Results: 111 LC patients have been enrolled to date; with 78 receiving at least one vaccination and 33 unvaccinated. Median age is 69, with 58% female. 39 patients were fully vaccinated (defined as 14+ days after second vaccination). Partially vaccinated (after 1 st vaccine dose) LC patients had a lower median antibody level than partially vaccinated HCs (p¼0.01). Fully vaccinated LC patients had substantial antibody titers but a lower median antibody level than fully vaccinated HCs (p¼0.01) with a subset not raising large antibody titers. Especially important were the 30% of partially vaccinated LC patients who did not develop neutralizing antibodies. To date, there were no significant differences in median antibody levels in LC patients by gender, smoking status, age (< or > 65 years old), or treatment (with or without chemotherapy, immune checkpoint inhibitors, or targeted therapy). Conclusion: While most (w70%+) of LC patients mounted a good antibody response to vaccination, a subgroup had significantly lower anti-spike antibody/neutralizing levels compared to controls. Further studies are required to evaluate the role of further boost vaccinations in this patient population with a particular focus on patients not producing neutralizing antibodies to further understand the lack of response. We will continue to analyze the effect of systemic anti-cancer therapies as more data becomes available. Keywords: SARS-CoV-2, lung cancer, covid-19 OA01.02 Impact of COVID-19 Outbreak on Lung Cancer Diagnosis and Continuum of Care: Data From an Italian Multicenter Study

10 E. Rijavec, 11 R. Chiari, 12 S. Oldani, 13 A. Caglio

Rome/IT, 5 Medical Oncology Unit, Careggi University Hospital, Firenze/IT, 6 Pneumo-Oncology Unit, Monaldi Hospital, Napoli/ IT, 7 Medical Oncology, A.O. Papardo & Department of Human Pathology, University of Messina, Messina/IT, 8 Medical Oncology, Irccs Ospedale Policlinico San Martino, Genova/IT, 9 Thoracic Medical Oncology, Istituto Nazionale Tumori -Irccs -Fondazione G. Pascale, Naples/IT, 10 Oncology Unit, Irccs Ospedale Sacro Cuore Don Calabria Negrar, Verona/IT, 11 Medical Oncology, Fondazione Irccs Ca' Granda Ospedale Maggiore Policlinico, Milano/IT, 12 Medical Oncology, Ospedali Riuniti Padova Sud "madre Teresa Di Calcutta