Reduced humoral immune response after BNT162b2 coronavirus disease 2019 messenger RNA vaccination in cancer patients under antineoplastic treatment.

BACKGROUND: Cancer patients are at a higher risk of developing severe coronavirus disease 2019 (COVID-19). However, the safety and efficacy of COVID-19 vaccination in cancer patients undergoing treatment remain unclear. PATIENTS AND METHODS: In this interventional prospective multicohort study, priming and booster doses of the BNT162b2 COVID-19 vaccine were administered 21 days apart to solid tumor patients receiving chemotherapy, immunotherapy, targeted or hormonal therapy, and patients with a hematologic malignancy receiving rituximab or after allogeneic hematopoietic stem cell transplantation. Vaccine safety and efficacy (until 3 months post-booster) were assessed. Anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) receptor-binding domain (RBD) antibody levels were followed over time (until 28 days after the booster) and in vitro SARS-CoV-2 50% neutralization titers (NT50) toward the wild-type Wuhan strain were analyzed 28 days after the booster. RESULTS: Local and systemic adverse events (AEs) were mostly mild to moderate (only 1%-3% of patients experienced severe AEs). Local, but not systemic, AEs occurred more frequently after the booster dose. Twenty-eight days after the booster vaccination of 197 cancer patients, RBD-binding antibody titers and NT50 were lower in the chemotherapy group {234.05 IU/ml [95% confidence interval (CI) 122.10-448.66] and 24.54 (95% CI 14.50-41.52), respectively} compared with healthy individuals [1844.93 IU/ml (95% CI 1383.57-2460.14) and 122.63 (95% CI 76.85-195.67), respectively], irrespective of timing of vaccination during chemotherapy cycles. Extremely low antibody responses were seen in hematology patients receiving rituximab; only two patients had RBD-binding antibody titers necessary for 50% protection against symptomatic SARS-CoV-2 infection (<200 IU/ml) and only one had NT50 above the limit of detection. During the study period, five cancer patients tested positive for SARS-CoV-2 infection, including a case of severe COVID-19 in a patient receiving rituximab, resulting in a 2-week hospital admission. CONCLUSION: The BNT162b2 vaccine is well-tolerated in cancer patients under active treatment. However, the antibody response of immunized cancer patients was delayed and diminished, mainly in patients receiving chemotherapy or rituximab, resulting in breakthrough infections.

Ambulatory follow-up care and monitoring of cancer patients during SARS-CoV-2 pandemic by collecting blood samples at home and monitoring systemic therapy using a smartphone application (COREO-trial)

Background: There is a broad range of clinical presentations of a SARS-CoV-2 viral infection varying from asymptomatic, sensation of a mild cold or flu to severe bilateral pneumonia and death. Liang et al. already reported the most severe complications in cancer patients particularly when they had undergone chemotherapy or surgery over the last month. In absence of a vaccine or adequate treatment of COVID-19 current measures to minimize the infectious risk of SARS-CoV-2 in a cancer patient population are focused on social distancing and protective measures for the medical and nursing staff members, and in some settings also patients. As it is clear that a hospital is a high risk setting to contract COVID-19, one of the strategies we can use to treat cancer patients as safe as possible, is to reduce hospital visits to a strict minimum. Trial design: The COREO-trial is a non-randomized cohort study at the Oncology unit of the Antwerp University Hospital (COVID-19 reference center) and AZ Maria Middelares Gent, both in Belgium. This trial contains two groups. Group A consists of patients that undergo outpatient monitoring (blood sampling at home and monitoring side effects using a smartphone application). Group B consists of patients that are in the classical hospital setting (= control group). The primary objective is to assess whether patients having home monitored oncologic treatment (cohort A) have a lower risk to the develop (severe) clinical COVID-19 compared to patients having classic in hospital oncologic treatment (cohort B). The working hypothesis is that interactive outpatient monitoring and management within the COREO-trial allows high quality cancer care with reduction of COVID-19 related complications. Legal entity responsible for the study: Antwerp University Hospital. Funding: Antwerp University Hospital. Disclosure: All authors have declared no conflicts of interest.

Expected medium and long term impact of the COVID-19 outbreak in oncology

Background: The ongoing SARS-CoV-2 pandemic and ensuing coronavirus disease (COVID-19) is challenging cancer care and services worldwide. Methods: A 95 items survey was distributed worldwide by 20 oncologists from 10 of the most affected countries in order to evaluate the impact on organization of oncological care. Results: 109 representatives from oncology centers in 18 countries (62.4% academic hospitals) filled out the survey (June 17 – July 14, 2020). A swab or gargle test is systematically performed before day care unit or overnight stay admissions in 27.5% and 58.7% of the centers, respectively. A local registry (64.2%) and systematic tracing (77.1%) of infected patients was organized in many centers. Treatment modalities mostly affected by the pandemic (cancellation/delay) were surgery (44.1%) and chemotherapy (25.7%). Earlier cessation of palliative treatment was observed in 32.1% of centers, and 64.2 % of participants agree that under-treatment is a major concern. At the pandemic peak, teleconsultations were performed for follow-up (94.5%), for oral therapy (92.7%), but also for patients receiving immunotherapy (57.8%) or chemotherapy (55%). Approximately 82% of participants estimate that they will continue to use telemedicine. Most participants reported more frequent use of virtual tumor boards (82%) and oncological team meetings (92%), but 45% disagree that virtual meetings are an acceptable alternative to live international meetings. Although 60.9% report reduced clinical activity during the pandemic peak, only 28.4% had an increased scientific activity. Only 18% of participants estimate that their well-being will not recover to previous levels by the end of the year;63% indicate easily accessible psychological support for caregivers, but only 10% used or planned to use it. All clinical trial activities are or will soon be reactivated in 72.5% of the centers. Major study protocol violations/deviations were observed in 27.5% and significant reductions of clinical trial activities are expected by 37% of centers this year. Conclusions: COVID-19 has a major impact on organization of patient care, well-being of caregivers, continued medical education and clinical trial activities in oncology. Legal entity responsible for the study: The authors. Funding: Fondation Léon Fredericq. Disclosure: G. Jerusalem: Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Novartis;Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Roche;Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Pfizer;Advisory/Consultancy, Travel/Accommodation/Expenses: Lilly;Advisory/Consultancy, Travel/Accommodation/Expenses: Amgen;Advisory/Consultancy, Travel/Accommodation/Expenses: BMS;Advisory/Consultancy, Travel/Accommodation/Expenses: AstraZeneca;Advisory/Consultancy, Travel/Accommodation/Expenses: Daiichi Sankyo;Advisory/Consultancy: AbbVie;Travel/Accommodation/Expenses: MedImmune;Travel/Accommodation/Expenses: Merck KGaA. G. Curigliano: Advisory/Consultancy, Speaker Bureau/Expert testimony: Roche;Advisory/Consultancy, Speaker Bureau/Expert testimony: Seattle Genetics;Speaker Bureau/Expert testimony, Writing engagement: Novartis;Advisory/Consultancy, Speaker Bureau/Expert testimony: Lilly;Advisory/Consultancy, Speaker Bureau/Expert testimony: Pfizer;Advisory/Consultancy, Speaker Bureau/Expert testimony: Foundation Medicine;Advisory/Consultancy, Speaker Bureau/Expert testimony: Samsung;Advisory/Consultancy, Speaker Bureau/Expert testimony: Celltrion;Leadership role, Scientific Affairs Group: Ellipsis;Speaker Bureau/Expert testimony, Writing engagement: BMS;Speaker Bureau/Expert testimony: MSD;Advisory/Consultancy: Mylan. M. Campone: Honoraria (self), Advisory/Consultancy: GT1;Honoraria (institution), Advisory/Consultancy: Sanofi;Honoraria (institution), Advisory/Consultancy: Pierre-Favre;Honoraria (institution), Advisory/Consultancy: AstraZeneca;Honoraria (institution), Advisory/Consultancy: Servi r;Honoraria (institution), Advisory/Consultancy, Speaker Bureau/Expert testimony: Novartis;Honoraria (institution), Advisory/Consultancy: AbbVie;Honoraria (institution), Advisory/Consultancy: Accord;Honoraria (institution), Advisory/Consultancy: Pfizer;Speaker Bureau/Expert testimony: Lilly. M. Martin: Advisory/Consultancy, Research grant/Funding (institution): Roche;Advisory/Consultancy, Research grant/Funding (institution): Novartis;Advisory/Consultancy, Research grant/Funding (institution): Puma;Advisory/Consultancy: AstraZeneca;Advisory/Consultancy: Amgen;Advisory/Consultancy: Taiho Oncology;Advisory/Consultancy: Daichii Sankyo;Advisory/Consultancy: PharmaMar;Advisory/Consultancy: Eli Lilly;Advisory/Consultancy: Pfizer. M. Cristofanilli: Advisory/Consultancy: CytoDyn;Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Pfizer;Advisory/Consultancy: Lilly;Advisory/Consultancy: Novartis;Advisory/Consultancy, Speaker Bureau/Expert testimony: Foundation Medicine;Advisory/Consultancy: G1 Therapeutics;Advisory/Consultancy: Sermionexx;Advisory/Consultancy: Genentch. L. Pusztai: Honoraria (self), Research grant/Funding (institution), Clinical trial support: Merck;Honoraria (self), Research grant/Funding (institution), Clinical trial support: AstraZeneca;Honoraria (self), Research grant/Funding (institution), Clinical trial support: Seattle Genetics;Honoraria (self): Novartis;Honoraria (self), Research grant/Funding (institution), Clinical trial support: Roche Genentech;Honoraria (self): Eisai;Honoraria (self): Daiichi;Honoraria (self): Syndax;Honoraria (self): Immunomedics. R. Bartsch: Advisory/Consultancy: Accord;Honoraria (self): AstraZeneca;Advisory/Consultancy, Research grant/Funding (institution): Daiichi;Advisory/Consultancy, Travel/Accommodation/Expenses: Eli-Lilly;Advisory/Consultancy, Travel/Accommodation/Expenses: MSD;Advisory/Consultancy, Research grant/Funding (institution): Novartis;Advisory/Consultancy, Research grant/Funding (institution): Roche;Advisory/Consultancy: Puma;Advisory/Consultancy: Pierre-Favre;Advisory/Consultancy: Sandoz;Advisory/Consultancy: Eisai. M. Tagliamento: Travel/Accommodation/Expenses: Roche;Travel/Accommodation/Expenses: Bristol-Myers Squibb;Travel/Accommodation/Expenses: AstraZeneca;Travel/Accommodation/Expenses: Takeda;Travel/Accommodation/Expenses: Novartis;Travel/Accommodation/Expenses: Amgen. J. Cortés: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Roche;Honoraria (self), Advisory/Consultancy: Celgene;Advisory/Consultancy: Cellestia;Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca;Advisory/Consultancy: Biothera Pharmaceutical;Advisory/Consultancy: Merus;Advisory/Consultancy: Seattle Genetics;Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Daiichi Sankyo;Advisory/Consultancy: Erytech;Advisory/Consultancy: Athenex + Polyphor;Advisory/Consultancy, Shareholder/Stockholder/Stock options: MedSIR;Honoraria (self), Advisory/Consultancy: Lilly;Advisory/Consultancy: Servier;Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Merck Sharp Dome;Advisory/Consultancy: GSK;Advisory/Consultancy: Leuko;Advisory/Consultancy: Bioasis;Advisory/Consultancy: Clovis Oncology;Advisory/Consultancy: Boehringer Ingelheim;Honoraria (self), Travel/Accommodation/Expenses: Novartis;Honoraria (self), Travel/Accommodation/Expenses: Eisai;Honoraria (self), Research grant/Funding (institution), Travel/Accommodation/Expenses: Pfizer;Honoraria (self): Samsung Bioepis;Research grant/Funding (institution): Ariad Pharmaceuticals;Research grant/Funding (institution): Baxalta GMBH/Servier Affaires;Research grant/Funding (institution): Bayer Healthcare;Research grant/Funding (institution): F. Hoffmann-La Roche;Research grant/Funding (institution): Guardanth Health;Research grant/Funding (institution): Piqur THerapeutics;Research grant/Funding (institution): Puma C;Research grant/ unding (institution): Queen Mary University of London. E.M. Ciruelos: Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Roche;Advisory/Consultancy, Speaker Bureau/Expert testimony: Lilly;Advisory/Consultancy, Speaker Bureau/Expert testimony: Novartis;Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Pfizer. H.S. Rugo: Research grant/Funding (institution): Eisai;Research grant/Funding (institution): Genentech;Research grant/Funding (institution): Lilly;Research grant/Funding (institution), Travel/Accommodation/Expenses: MacroGenics;Research grant/Funding (institution): Merck;Research grant/Funding (institution), Travel/Accommodation/Expenses: Novartis;Research grant/Funding (institution): Obi Pharma;Research grant/Funding (institution): Odonate Therapeutics;Research grant/Funding (institution): Immunomedics;Research grant/Funding (institution), Travel/Accommodation/Expenses: Daiichi-Sankyo;Research grant/Funding (institution), Travel/Accommodation/Expenses: Pfizer;Advisory/Consultancy: Samsung;Advisory/Consultancy: Celtrion;Travel/Accommodation/Expenses: Mylan;Travel/Accommodation/Expenses: AstraZeneca. All other authors have declared no conflicts of interest.