Immunogenicity and Safety of the BNT162b2 mRNA COVID-19 Vaccine in Patients with Melanoma Treated with Immunotherapy

Simple Summary The efficacy and safety of the BNT126b2 vaccine against SARS-CoV-2 has not been thoroughly studied in cancer patients treated with immunotherapy. This research aims to investigate the efficacy and safety of the vaccine in patients with melanoma under immunotherapy; at the same time, through the immunophenotyping of T cells and myeloid cells of the peripheral blood, it will be possible to look for changes in the subpopulations of such cells after vaccinations. The results of the study help establish the efficacy and safety of the vaccine in this population, especially since a theoretical concern exists about the vaccine triggering irAEs. Abstract The BNT162b2 vaccine against SARS-CoV-2 has a proven efficacy and a favorable safety profile. In cancer patients under immunotherapy in the form of immune-checkpoint inhibitors (ICIs), the efficacy of the vaccine has not been thoroughly studied, while a theoretical concern has also been raised about triggering immune-related adverse events (irAEs) by the vaccine. We conducted a prospective, non-interventional study on the immunogenicity and safety of the BNT162b2 vaccine in patients with advanced or metastatic melanoma treated with ICIs. Blood samples were obtained 0–4 days before the first dose and 12–21 days after the second dose of the vaccine for the quantification of the SARS-CoV-2 anti-spike antibody using an ELISA and immunophenotyping of the T and myeloid cell subpopulations. The active recording of AEs for a two-month period was conducted. Forty patients were included in the study. All but one (97.3%) achieved seroconversion after two doses of the vaccine and no correlations of the antibody titers with any of the studied parameters (age, gender, stage and duration of the disease, type of ICI, previous treatment, etc.) were found. Moreover, no differences in the subpopulations of the T cells (including the T-regulatory cells) or the myeloid cells were found pre- and post-vaccination. All AEs were low-grade, while one case of arthritis exacerbation was noted. The seroconversion rate in the studied population was high and was comparable to that of healthy subjects, while no major safety issues were raised during the safety follow-up. Finally, no derangements in the subpopulations of T cells or myeloid cells were noted. This is the first study focusing on the immunogenicity, safety, and effect of anti-SARS-CoV-2 vaccines on the blood-cell immunophenotype status of patients with melanoma treated with ICIs.

[1]  A. Schneeweiss,et al.  Cytokine release syndrome-like serum responses after COVID-19 vaccination are frequent and clinically inapparent under cancer immunotherapy , 2022, Nature Cancer.

[2]  Yang Xie,et al.  Association between immune-related adverse event timing and treatment outcomes , 2022, Oncoimmunology.

[3]  J. Hassel,et al.  Immune-related adverse events of COVID-19 vaccination in skin cancer patients receiving immune-checkpoint inhibitor treatment , 2021, Cancer Immunology, Immunotherapy.

[4]  Robin L. Jones,et al.  Adaptive immunity and neutralizing antibodies against SARS-CoV-2 variants of concern following vaccination in patients with cancer: The CAPTURE study , 2021, Nature Cancer.

[5]  S. Gandini,et al.  Predictors of poor seroconversion and adverse events to SARS-CoV-2 mRNA BNT162b2 vaccine in cancer patients on active treatment , 2021, European Journal of Cancer.

[6]  F. Baldanti,et al.  A snapshot of the immunogenicity, efficacy and safety of a full course of BNT162b2 anti-SARS-CoV-2 vaccine in cancer patients treated with PD-1/PD-L1 inhibitors: a longitudinal cohort study , 2021, ESMO Open.

[7]  H. Ulmer,et al.  Serological SARS‐CoV‐2 antibody response, potential predictive markers and safety of BNT162b2 mRNA COVID‐19 vaccine in haematological and oncological patients , 2021, British journal of haematology.

[8]  Z. K. Lu,et al.  Age and Gender Disparities in Adverse Events Following COVID-19 Vaccination: Real-World Evidence Based on Big Data for Risk Management , 2021, Frontiers in Medicine.

[9]  K. Pradhan,et al.  Seroconversion rates following COVID-19 vaccination among patients with cancer , 2021, Cancer Cell.

[10]  M. Dimopoulos,et al.  Low titers of SARS-CoV-2 neutralizing antibodies after first vaccination dose in cancer patients receiving checkpoint inhibitors , 2021, Journal of Hematology & Oncology.

[11]  L. Pickering,et al.  Cytokine release syndrome in a patient with colorectal cancer after vaccination with BNT162b2 , 2021, Nature Medicine.

[12]  D. McGovern,et al.  Adverse Events After SARS-CoV-2 mRNA Vaccination Among Patients With Inflammatory Bowel Disease , 2021, The American journal of gastroenterology.

[13]  Xiaocheng Wu,et al.  Indications for and contraindications of immune checkpoint inhibitors in cancer patients with coronavirus disease 2019 vaccination , 2021, Future oncology.

[14]  B. Waissengrin,et al.  Short-term safety of the BNT162b2 mRNA COVID-19 vaccine in patients with cancer treated with immune checkpoint inhibitors , 2021, The Lancet Oncology.

[15]  B. Graham,et al.  T cell immunity to SARS-CoV-2 following natural infection and vaccination , 2020, Biochemical and Biophysical Research Communications.

[16]  F. Roohvand,et al.  Severe acute respiratory syndrome‐coronavirus‐2 spike (S) protein based vaccine candidates: State of the art and future prospects , 2020, Reviews in medical virology.

[17]  P. Dormitzer,et al.  COVID-19 vaccine BNT162b1 elicits human antibody and TH1 T cell responses , 2020, Nature.

[18]  X. Cui,et al.  COVID-19 in cancer patients: risk, clinical features, and management , 2020, Cancer biology & medicine.

[19]  B. Keam,et al.  Cell-Mediated Immunogenicity of Influenza Vaccination in Patients with Cancer Receiving Immune Checkpoint Inhibitors. , 2020, The Journal of infectious diseases.

[20]  Zhiquan Hu,et al.  Clinical characteristics and risk factors associated with COVID-19 disease severity in patients with cancer in Wuhan, China: a multicentre, retrospective, cohort study , 2020, The Lancet Oncology.

[21]  Alokkumar Jha,et al.  Clinical impact of COVID-19 on patients with cancer (CCC19): a cohort study , 2020, The Lancet.

[22]  D. Kerr,et al.  COVID-19 mortality in patients with cancer on chemotherapy or other anticancer treatments: a prospective cohort study , 2020, The Lancet.

[23]  M. Suarez‐Almazor,et al.  Immune-related adverse events of checkpoint inhibitors , 2020, Nature Reviews Disease Primers.

[24]  Dong-Wan Kim,et al.  Immunogenicity of influenza vaccination in patients with cancer receiving immune checkpoint inhibitor. , 2020, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[25]  J. Wolchok,et al.  Safety of Inactivated Influenza Vaccine in Cancer Patients Receiving Immune Checkpoint Inhibitors (ICI). , 2019, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[26]  F. Stenner,et al.  Influenza vaccination of cancer patients during PD-1 blockade induces serological protection but may raise the risk for immune-related adverse events , 2018, Journal of Immunotherapy for Cancer.

[27]  Robert Weissert,et al.  Peripheral Blood Mononuclear Cells: Isolation, Freezing, Thawing, and Culture. , 2016, Methods in molecular biology.

[28]  C. Kurts,et al.  Regulatory T cells use programmed death 1 ligands to directly suppress autoreactive B cells in vivo , 2012, Proceedings of the National Academy of Sciences.

[29]  L. Picker,et al.  Mapping T cell epitopes by flow cytometry. , 2003, Methods.