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      Immunogenicity of COVID-19 Vaccination in Melanoma Patients under Immune Checkpoint Blockade

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          Abstract

          Background

          Immunogenicity of SARS-CoV-2 vaccines is modestly impaired in cancer patients due to a generally weakened immune system. Immune checkpoint inhibitors (ICI) are expected to enhance immune response. This has already been described to be the case in influenza vaccines, and first data about COVID-19 vaccines show a trend in this direction.

          Aim

          We aimed to investigate the immune response of patients with melanoma under ICI therapy after COVID-19 vaccination.

          Patients and Methods

          In the Skin Cancer Center Hanover (Germany), we recruited 60 patients with advanced melanoma who either received ICI therapy during or before the vaccination period. Serological blood analysis was performed using quantitative ELISA for Anti-SARS-CoV-2 spike protein 1 IgG antibodies.

          Results

          We did not observe an enhanced humoral immune response in patients under active or past ICI therapy after COVID-19 vaccination. Nevertheless, there is a tendency of higher antibody levels when ICI therapy was received within the last 6 months before vaccination. Subgroup analysis revealed that patients in our study population under ongoing targeted therapy during vaccination period had significantly higher median antibody levels than patients without any active antitumor treatment.

          Conclusion

          Melanoma patients under ICI therapy show comparable antibody response after SARS-CoV-2 vaccination to healthy health care professionals. This finding is independent of the timing of ICI therapy.

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          Most cited references17

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          Cancer patients in SARS-CoV-2 infection: a nationwide analysis in China

          China and the rest of the world are experiencing an outbreak of a novel betacoronavirus known as severe acute respiratory syndrome corona virus 2 (SARS-CoV-2). 1 By Feb 12, 2020, the rapid spread of the virus had caused 42 747 cases and 1017 deaths in China and cases have been reported in 25 countries, including the USA, Japan, and Spain. WHO has declared 2019 novel coronavirus disease (COVID-19), caused by SARS-CoV-2, a public health emergency of international concern. In contrast to severe acute respiratory system coronavirus and Middle East respiratory syndrome coronavirus, more deaths from COVID-19 have been caused by multiple organ dysfunction syndrome rather than respiratory failure, 2 which might be attributable to the widespread distribution of angiotensin converting enzyme 2—the functional receptor for SARS-CoV-2—in multiple organs.3, 4 Patients with cancer are more susceptible to infection than individuals without cancer because of their systemic immunosuppressive state caused by the malignancy and anticancer treatments, such as chemotherapy or surgery.5, 6, 7, 8 Therefore, these patients might be at increased risk of COVID-19 and have a poorer prognosis. On behalf of the National Clinical Research Center for Respiratory Disease, we worked together with the National Health Commission of the People's Republic of China to establish a prospective cohort to monitor COVID-19 cases throughout China. As of the data cutoff on Jan 31, 2020, we have collected and analysed 2007 cases from 575 hospitals (appendix pp 4–9 for a full list) in 31 provincial administrative regions. All cases were diagnosed with laboratory-confirmed COVID-19 acute respiratory disease and were admitted to hospital. We excluded 417 cases because of insufficient records of previous disease history. 18 (1%; 95% CI 0·61–1·65) of 1590 COVID-19 cases had a history of cancer, which seems to be higher than the incidence of cancer in the overall Chinese population (285·83 [0·29%] per 100 000 people, according to 2015 cancer epidemiology statistics 9 ). Detailed information about the 18 patients with cancer with COVID-19 is summarised in the appendix (p 1). Lung cancer was the most frequent type (five [28%] of 18 patients). Four (25%) of 16 patients (two of the 18 patients had unknown treatment status) with cancer with COVID-19 had received chemotherapy or surgery within the past month, and the other 12 (25%) patients were cancer survivors in routine follow-up after primary resection. Compared with patients without cancer, patients with cancer were older (mean age 63·1 years [SD 12·1] vs 48·7 years [16·2]), more likely to have a history of smoking (four [22%] of 18 patients vs 107 [7%] of 1572 patients), had more polypnea (eight [47%] of 17 patients vs 323 [23%] of 1377 patients; some data were missing on polypnea), and more severe baseline CT manifestation (17 [94%] of 18 patients vs 1113 [71%] of 1572 patients), but had no significant differences in sex, other baseline symptoms, other comorbidities, or baseline severity of x-ray (appendix p 2). Most importantly, patients with cancer were observed to have a higher risk of severe events (a composite endpoint defined as the percentage of patients being admitted to the intensive care unit requiring invasive ventilation, or death) compared with patients without cancer (seven [39%] of 18 patients vs 124 [8%] of 1572 patients; Fisher's exact p=0·0003). We observed similar results when the severe events were defined both by the above objective events and physician evaluation (nine [50%] of 18 patients vs 245 [16%] of 1572 patients; Fisher's exact p=0·0008). Moreover, patients who underwent chemotherapy or surgery in the past month had a numerically higher risk (three [75%] of four patients) of clinically severe events than did those not receiving chemotherapy or surgery (six [43%] of 14 patients; figure ). These odds were further confirmed by logistic regression (odds ratio [OR] 5·34, 95% CI 1·80–16·18; p=0·0026) after adjusting for other risk factors, including age, smoking history, and other comorbidities. Cancer history represented the highest risk for severe events (appendix p 3). Among patients with cancer, older age was the only risk factor for severe events (OR 1·43, 95% CI 0·97–2·12; p=0·072). Patients with lung cancer did not have a higher probability of severe events compared with patients with other cancer types (one [20%] of five patients with lung cancer vs eight [62%] of 13 patients with other types of cancer; p=0·294). Additionally, we used a Cox regression model to evaluate the time-dependent hazards of developing severe events, and found that patients with cancer deteriorated more rapidly than those without cancer (median time to severe events 13 days [IQR 6–15] vs 43 days [20–not reached]; p<0·0001; hazard ratio 3·56, 95% CI 1·65–7·69, after adjusting for age; figure). Figure Severe events in patients without cancer, cancer survivors, and patients with cancer (A) and risks of developing severe events for patients with cancer and patients without cancer (B) ICU=intensive care unit. In this study, we analysed the risk for severe COVID-19 in patients with cancer for the first time, to our knowledge; only by nationwide analysis can we follow up patients with rare but important comorbidities, such as cancer. We found that patients with cancer might have a higher risk of COVID-19 than individuals without cancer. Additionally, we showed that patients with cancer had poorer outcomes from COVID-19, providing a timely reminder to physicians that more intensive attention should be paid to patients with cancer, in case of rapid deterioration. Therefore, we propose three major strategies for patients with cancer in this COVID-19 crisis, and in future attacks of severe infectious diseases. First, an intentional postponing of adjuvant chemotherapy or elective surgery for stable cancer should be considered in endemic areas. Second, stronger personal protection provisions should be made for patients with cancer or cancer survivors. Third, more intensive surveillance or treatment should be considered when patients with cancer are infected with SARS-CoV-2, especially in older patients or those with other comorbidities.
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            iRECIST: guidelines for response criteria for use in trials testing immunotherapeutics

            Tumours respond differently to immunotherapies compared with chemotherapeutic drugs, raising questions about the assessment of changes in tumour burden—a mainstay of evaluation of cancer therapeutics that provides key information about objective response and disease progression. A consensus guideline—iRECIST—was developed by the RECIST working group for the use of modified Response Evaluation Criteria in Solid Tumours (RECIST version 1.1) in cancer immunotherapy trials, to ensure consistent design and data collection, facilitate the ongoing collection of trial data, and ultimate validation of the guideline. This guideline describes a standard approach to solid tumour measurements and definitions for objective change in tumour size for use in trials in which an immunotherapy is used. Additionally, it defines the minimum datapoints required from future trials and those currently in development to facilitate the compilation of a data warehouse to use to later validate iRECIST. An unprecedented number of trials have been done, initiated, or are planned to test new immune modulators for cancer therapy using a variety of modified response criteria. This guideline will allow consistent conduct, interpretation, and analysis of trials of immunotherapies.
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              Adjuvant Nivolumab versus Ipilimumab in Resected Stage III or IV Melanoma

              Nivolumab and ipilimumab are immune checkpoint inhibitors that have been approved for the treatment of advanced melanoma. In the United States, ipilimumab has also been approved as adjuvant therapy for melanoma on the basis of recurrence-free and overall survival rates that were higher than those with placebo in a phase 3 trial. We wanted to determine the efficacy of nivolumab versus ipilimumab for adjuvant therapy in patients with resected advanced melanoma.
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                Author and article information

                Journal
                Oncology
                Oncology
                OCL
                Oncology
                S. Karger AG (Allschwilerstrasse 10, P.O. Box · Postfach · Case postale, CH–4009, Basel, Switzerland · Schweiz · Suisse, Phone: +41 61 306 11 11, Fax: +41 61 306 12 34, karger@karger.com )
                0030-2414
                1423-0232
                24 May 2022
                24 May 2022
                : 1-7
                Affiliations
                [1] aDepartment of Rheumatology and Immunology, Hanover Medical School, Hannover, Germany
                [2] bDean's Office − Curriculum Development, Hannover Medical School, Hannover, Germany
                [3] cCiiM − Center for Individualized Infection Medicine, Hannover, Germany
                [4] dInstitute for Information Engineering, Ostfalia University of Applied Sciences, Wolfenbüttel, Germany
                [5] eDepartment of Dermatology, Johannes Wesling Medical Center Minden, Ruhr University Bochum, Minden, Germany
                [6] fDepartment of General Practice, University Medical Center Göttingen, Göttingen, Germany
                [7] gGerman Center for Infection Research (DZIF), partner site Hannover-Braunschweig, Hannover-Braunschweig, Germany
                [8] hDepartment of Dermatology and Allergy, Skin Cancer Center Hannover, Hanover Medical School, Hannover, Germany
                Author notes
                Article
                ocl-0001
                10.1159/000524894
                9393793
                35609553
                2c33c1c5-b6da-41db-96e9-986f71a96f27
                Copyright © 2022 by S. Karger AG, Basel

                This article is licensed under the Creative Commons Attribution 4.0 International License (CC BY). Usage, derivative works and distribution are permitted provided that proper credit is given to the author and the original publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                History
                : 2 March 2022
                : 6 April 2022
                Page count
                Figures: 2, Tables: 2, References: 18, Pages: 7
                Categories
                Clinical Study

                covid-19 vaccination,advanced melanoma,immune checkpoint inhibitors,immunogenicity,sars-cov-2

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