==== Front Cancer Med Cancer Med 10.1002/(ISSN)2045-7634 CAM4 Cancer Medicine 2045-7634 John Wiley and Sons Inc. Hoboken 37114577 10.1002/cam4.5968 CAM45968 CAM4-2022-12-5517.R2 Research Article RESEARCH ARTICLES Clinical Cancer Research Clinical efficacy of the first two doses of anti‐SARS‐CoV‐2 mRNA vaccines in solid cancer patients Cona et al. Cona Maria Silvia https://orcid.org/0000-0002-1838-7819 1 Riva Agostino 2 3 Dalu Davide 1 Gabrieli Arianna 3 Fasola Cinzia 1 Lipari Giuseppe 3 Pozza Giacomo 2 Rulli Eliana 4 Galli Francesca 4 Ruggieri Lorenzo https://orcid.org/0000-0002-9972-2761 1 ruggieri.lorenzo@asst-fbf-sacco.it Masedu Elsa 1 Parma Gaia 1 Chizzoniti Davide 1 Gambaro Anna 1 Ferrario Sabrina 1 Antista Maria 1 De Monte Matteo 1 Tarkowski Maciej S. 3 La Verde Nicla 1 1 Department of Oncology Sacco Hospital, ASST Fatebenefratelli Sacco Milan Italy 2 Department of Infectious Diseases, Sacco Hospital ASST Fatebenefratelli Sacco Milan Italy 3 Luigi Sacco Department of Biomedical and Clinical Sciences DIBIC University of Milan Milan Italy 4 Laboratory of Methodology for Clinical Research Istituto di Ricerche Farmacologiche Mario Negri IRCCS Milan Italy * Correspondence Lorenzo Ruggieri, Department of Oncology, University Hospital Luigi Sacco ‐ ASST Fatebenefratelli Sacco, Via G.B. Grassi, 74. 20157 Milan, Italy. Email: ruggieri.lorenzo@asst-fbf-sacco.it 28 4 2023 6 2023 12 12 10.1002/cam4.v12.12 1296712974 30 3 2023 17 12 2022 06 4 2023 © 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd. https://creativecommons.org/licenses/by/4.0/ This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. Abstract Introduction Cancer patients are frail individuals, thus the prevention of SARS‐CoV‐2 infection is essential. To date, vaccination is the most effective tool to prevent COVID‐19. In a previous study, we evaluated the immunogenicity of two doses of mRNA‐based vaccines (BNT162b2 or mRNA‐1273) in solid cancer patients. We found that seroconversion rate in cancer patients without a previous exposure to SARS‐CoV‐2 was lower than in healthy controls (66.7% vs. 95%, p = 0.0020). The present study aimed to evaluate the clinical efficacy of the vaccination in the same population. Methods This is a single‐institution, prospective observational study. Data were collected through a predefined questionnaire through phone call in the period between the second and third vaccine dose. The primary objective was to describe the clinical efficacy of the vaccination, defined as the percentage of vaccinated subjects who did not develop symptomatic COVID‐19 within 6 months after the second dose. The secondary objective was to describe the clinical features of patients who developed COVID‐19. Results From January to June 2021, 195 cancer patients were enrolled. Considering that 7 (3.59%) patients tested positive for SARS‐CoV‐2 and 5 developed symptomatic disease, the clinical efficacy of the vaccination was 97.4%. COVID‐19 disease in most patients was mild and managed at home; only one hospitalization was recorded and no patient required hospitalization in the intensive care unit. Discussion Our study suggests that increasing vaccination coverage, including booster doses, could improve the prevention of infection, hospitalization, serious illness, and death in the frail population of cancer patients. Prevention of SARS‐CoV‐2 infection is crucial for cancer patients given their frailty and vaccination is the most effective method to achieve this goal. The present study aimed to evaluate the clinical efficacy of the first two doses of anti‐SARS‐CoV‐2 vaccines in treated solid cancer patients. The clinical efficacy was 97.4%. COVID‐19 disease in most patients was mild and managed at home; only one hospitalization was recorded and no patient required hospitalization in the intensive care unit. European Union's Horizon Europe Research and Innovation Actions101046041 source-schema-version-number2.0 cover-dateJune 2023 details-of-publishers-convertorConverter:WILEY_ML3GV2_TO_JATSPMC version:6.3.0 mode:remove_FC converted:03.07.2023 Cona MS , Riva A , Dalu D , et al. Clinical efficacy of the first two doses of anti‐SARS‐CoV‐2 mRNA vaccines in solid cancer patients. Cancer Med. 2023;12 :12967‐12974. doi:10.1002/cam4.5968 ==== Body pmc1 INTRODUCTION On March 11, 2020, the World Health Organization (WHO), after assessing the severity and global spread of SARS‐CoV‐2 infection, declared the status of global pandemic. 1 , 2 Since then, there have been more than 600,000,000 cases of coronavirus disease‐2019 (COVID‐19) and 6,500,000 deaths worldwide, of which 178,000 occurred in Italy. 3 To date, patients with cancer have showed an increase of SARS‐CoV‐2 infection rate (95% confidence interval [CI]: 8%–9%) with a twofold increased risk of adverse outcome (odds ratio [OR] for mortality 2.23, 95% CI: 1.82–2.94; intensive care unit [ICU] admission 2.39, 95% CI: 1.90–3.02) and severity of COVID‐19 (OR for hospitalization or severity of symptoms 2.08) compared to the general population. 4 , 5 , 6 , 7 , 8 In the early days of the COVID‐19 pandemic, the National Health Systems imposed a suspension of nonurgent medical services worldwide. Many studies reported a downscaling of cancer treatment with an increased risk of impaired efficacy. In addition, the delay in cancer diagnosis and treatment could have jeopardized patient prognosis and long‐term population outcomes. 9 , 10 , 11 , 12 Many medical oncologists tried to protect patients from nosocomial contagion, through the reorganization of hospital spaces and the application of all prevention and mitigation procedures (triage at the entrance, the use of individual protection devices, social distancing measures, etc.). Anyway, the real “ace up the sleeve” in the fight against SARS‐CoV‐2 was the vaccine. 13 In this dramatic scenario, the real change of course took place thanks to the launch of a global mass immunization strategy with anti‐SARS‐CoV‐2 vaccines. Since December 2020, Pfizer/BioNTech, AstraZeneca, and Moderna were among the first companies to develop anti‐COVID‐19 vaccines that were approved by the International Regulatory Agencies. From January 2021, the most important international oncology societies advocated for the high priority of vaccination in cancer patients, in order to attenuate the harmful consequences of the pandemic. Several studies in very heterogeneous populations of cancer patients evaluated the immunogenicity of one or two doses of COVID‐19 vaccine. 14 , 15 In a previous study, 16 we measured the antibody response to two doses of mRNA vaccines in solid cancer patients on active treatment. The seroconversion rate in patients with previous exposure to SARS‐CoV‐2 was comparable to that of healthy subjects (respectively 93.3% and 95%), but significantly lower in patients without previous infection (93.3% vs. 66.7%, p = 0.0020). Moreover, antibody response to vaccination negatively correlated with clinical variables of immune frailty, such as comorbidities, use of granulocyte‐colony stimulating factor (G‐CSF) and vaccine type. Besides, poor data are available in cancer population regarding the clinical efficacy of the vaccines, which is a parameter of protection from symptomatic disease. 17 The aim of the present study was to evaluate the clinical efficacy after two doses of mRNA‐based anti‐SARS‐CoV‐2 vaccines in the population enrolled in the aforementioned study. 16 2 MATERIALS AND METHODS This is a single‐institution, prospective observational study conducted from January to December 2021 at Luigi Sacco Hospital in Milan. We enrolled consecutive patients affected by solid malignancies, both in active treatment and in follow‐up, who received two doses of anti‐COVID‐19 vaccine (BNT162b2 [Comirnaty, BioNTech/Pfizer] or mRNA‐1273 [Spikevax, Moderna] vaccine). In the period between the second and third dose, patients were contacted through a phone call and were investigated with a predefined questionnaire in order to collect information regarding the clinical efficacy of vaccination. Demographic information, preexisting medical conditions, signs and symptoms, and clinical outcomes of a possible SARS‐CoV‐2 infection were recorded. The collected data were: Previous infection, demonstrated by nasopharyngeal swab testing for SARS‐CoV‐2 through reverse transcription‐polymerase chain reaction (PCR) or antigenic testing; COVID‐19 symptoms: fever ≥37.5°C, cough, rhinorrhea, sore throat, arthralgia/myalgia, gastrointestinal symptoms, and dysgeusia/dysosmia; Severity of the disease: asymptomatic, symptomatic managed at home, hospitalization, and admission in ICU; Therapies: non‐steroidal anti‐inflammatory drugs (NSAIDs)/paracetamol, antibiotics, hydroxychloroquine, low molecular weight heparin (LMWH), monoclonal antibodies, antiviral drugs, no treatment; Duration of COVID‐19 disease was defined as days from positive to negative SARS‐CoV‐2 test; it was stratified in the following three groups: 1–10 days, 11–30 days, or >30 days; Delayed anticancer treatment equal or greater than 7 days; Supposed source of infection: family/friends, public spaces, or hospital. The primary objective was to describe the clinical efficacy of vaccine, defined as the percentage of vaccinated subjects who did not develop symptomatic COVID‐19 within 6 months after the second dose. The secondary objective was to describe the clinical features of the patients who developed COVID‐19, in particular: possible sources of infection, symptoms, severity and duration of disease, treatment administered, delay in the administration of oncological therapy. The study protocol was conducted according to the principles of the Declaration of Helsinki. All the participants signed written informed consent before any study procedure. 3 RESULTS One‐hundred ninety‐five cancer patients who had received two doses of anti‐SARS‐CoV‐2 mRNA‐based vaccine were enrolled. The median age was 64.1 years (Q1–Q3: 53.8–72.0) and 70.8% of the patients were female. Breast was the most common tumor site (51.3%) and most of the patients had metastasis (67.2%). The BNT162b2 vaccine was administered in 71.8% of the subjects. Among 166 patients on active cancer treatment, the vaccine was injected after one or more cycles of therapy in 86.7% of the individuals. Traditional chemotherapy (33.3%) and targeted therapy alone (35.4%) represented the most used treatments. Forty‐four patients (22.6%) had more than one comorbid condition. Chronic steroid (duration of therapy ≥3 months) and G‐CSF use (at any dose and schedule) were reported in 45.1% and 7.7% of patients, respectively (Table 1). TABLE 1 Demographic and clinical features of cancer patients (n = 195). Tumor site n (%) Breast 100 (51.3) Gastroenteric 30 (15.4) Lung 24 (12.3) Genitourinary 15 (7.7) Gynecological 17 (8.7) Head and neck 2 (1.0) Other 7 (3.6) Tumor stage a n (%) Limited 62 (31.8) Advanced 131 (67.2) Therapy n (%) No therapy 28 (13.0) Chemotherapy 65 (30.2) Target therapy 69 (32.1) Chemotherapy + Target therapy 24 (11.2) Hormone therapy in metastatic disease 9 (4.2) Comorbidity n (%) No 86 (44.1) =1 65 (33.3) >1 44 (22.6) Steroids b n (%) Yes 88 (45.1) Granulocyte‐colony stimulating factor n (%) Yes 15 (7.7) Abbreviation: G‐CSF, granulocyte‐colony stimulating factor. a Not applicable for two patients. b Duration of therapy ≥3 months. During the study period, seven (3.59%) patients tested positive for SARS‐CoV‐2; five cases developed symptomatic disease. Based on these results, the clinical efficacy of two doses of mRNA‐based vaccines against COVID‐19 was 97.4% (5/195). The main characteristics of these seven patients are described in Table 2. Of note, none of them had COVID‐19 previously. Notably, among the group affected by symptomatic COVID‐19, three patients had not reached seroconversion after two doses of vaccine; the two seroconverted patients who developed symptomatic disease contracted the infection at least 5 months after administration of the second dose of vaccine. TABLE 2 Demographic and clinical features of the seven cancer patients infected by SARS‐CoV‐2 after two doses of mRNA‐based vaccines. Patient Symptomatic Asymptomatic 1 2 3 4 5 6 7 Age (years) 60 53 68 78 70 66 57 Sex M F F M M F F Type of vaccine mRNA‐1273 BNT162b2 BNT162b2 BNT162b2 mRNA‐1273 BNT162b2 mRNA‐1273 Tumor site Kaposi Sarcoma Breast Breast Lung Genitourinary Gastroenteric Breast Tumor stage Advanced Advanced Advanced Advanced Limited Limited Limited Vaccine administration before antiblastic therapy Yes Yes Yes No Yes No No Cancer treatment CT Target HT CT + Target No CT/Target CT CT + Target Steroid use Yes No No Yes No Yes Yes G‐CSF use No No No No No Yes No Comorbidity 1 0 1 > 1 1 1 0 Timing between second dose of vaccine and positive SARS‐CoV‐2 test (months) 5 3 7 6 4 7 9 Development of COVID‐19 symptoms Yes Yes Yes Yes Yes No No Seroconversion after two doses of vaccine Yes No No No Yes No Yes Abbreviations: CT, traditional chemotherapy; G‐CSF, granulocyte‐colony stimulating factor; HT, hormone therapy; Target, target therapy. The duration of COVID‐19 was 10 days in six patients; only in one patient the symptoms lasted for 30 days, causing the delay of over 7 days for the administration of oncological treatment. Only one symptomatic patient required hospitalization due to disease severity. No patient needed invasive ventilation or hospitalization in ICU. The other patients had mild illness and were managed at home and treated with ancillary and supportive therapy (NSAIDs or acetaminophen). Conversely, the only hospitalized patient received oxygen therapy, broad‐spectrum antibiotics, dexamethasone, remdesivir, and tocilizumab. The majority of infected patients estimated that the family members or friends were the possible source of infection (Table 3). TABLE 3 Characteristics of the clinical course of SARS‐CoV‐2 infection in 7 cancer patients after two doses of mRNA‐based vaccine. Symptoms Symptomatic patients Asymptomatic patients 1 2 3 4 5 6 7 Fever Yes No Yes Yes No No No Cough Yes Yes No Yes Yes No No Rhinorrhea No Yes No No Yes No No Sore throat No No Yes No Yes No No Arthralgia/myalgia No Yes Yes Yes No No No Gastroenteric symptoms No No No No No No No Dysgeusia/dysosmia No No No Yes Yes No No Duration (days) 11–30 1–10 1–10 1–10 1–10 1–10 1–10 Delayed cancer treatment ≥7 days Yes No No No No No No Therapy NSAIDs/paracetamol NSAIDs/paracetamol NSAIDs/paracetamol Oxygen Dexamethasone Antibiotics Remdesivir Tocilizumab NSAIDs/paracetamol NSAIDs/paracetamol NSAIDs/paracetamol Source of infection (referred) Family/friends Family/friends Hospital Family/friends Public space Family/friends Family/Friends Abbreviation: NSAIDs, non‐steroidal anti‐inflammatory drugs. 4 DISCUSSION The present study describes the clinical efficacy of two doses of SARS‐CoV‐2 mRNA‐based vaccines in a population of cancer patients both on active treatment and in follow‐up. After 6 months of follow‐up, 97.4% of patients did not develop COVID‐19. Our results are similar to those of previous studies that described a vaccine efficacy ranging from 62% to 94.4% before the emergence of the Omicron variants. This wide range was probably due to the heterogeneity of the research methodology. First, separate estimates of the effects of different variants of concern (VOCs) were not provided. In addition, the prevalence of VOCs was not considered, the study populations were not stratified according to the type of cancer (previous vs. active, solid vs. hematological) or timing of treatment (previous vs. ongoing treatment). 18 , 19 , 20 , 21 , 22 , 23 , 24 Prevention of the severe form of COVID‐19 (defined as hospitalization, ICU admission or severity of symptoms) is crucial for cancer patients and vaccination is an effective strategy for achieving this goal. 25 In this study, almost all of the patients (4 of 5 individuals) who developed COVID‐19 after the second vaccine dose had mild symptoms, for an average duration of 10 days, managed at home with symptomatic treatment. Published data suggest that cancer patients have a deeper waning of the antibody titers after the primary vaccination cycle compared to the general population. Approximately 6 months after the second dose, several cancer patients have undetectable anti‐spike antibodies. 26 It is noteworthy that in our study more than half of the patients infected by SARS‐CoV‐2 (57.1%) had not develop an adequate seroconversion after two vaccine doses, and all the patients but one developed SARS‐CoV‐2 infection over 4 months after the second vaccine. Therefore, they had probably reduced levels of neutralizing antibodies, thereby rendering them more prone to the infection. 16 On the other hand, patients who contracted the infection more than 6 months after the vaccination or who did not seroconvert after the second dose did not manifest any symptom. This observation suggests that, despite lack of humoral response to vaccination, a vaccine‐induced T‐cell response might protect from severe disease in patients receiving chemotherapy or immune checkpoint inhibitors. 27 , 28 This study has limitations. First, the implementation of extensive preventive measures by the Italian National Government during the observation period may have had a substantial effect on the observed low infection rates. In addition, it can be hypothesized that cancer patients and their caregivers, cognizant of their precarious state and apprehensive of contagion, may paid particular attention to the implementation of precautionary measures. 29 Furthermore, due to the emergency situation, not all patients have been tested by systematic nasopharyngeal swabs. An additional limitation of the study is the absence of data regarding the prevalence of the different SARS‐CoV‐2 variants that infected the patients who developed COVID‐19 after vaccination. Indeed, during the early stages of the COVID‐19 pandemic, the first two doses of anti‐SARS‐CoV‐2 mRNA vaccines were designed to target the original strain of the virus and its early variants. Besides, the epidemic periodical reports on SARS‐CoV‐2 variant dissemination in Italy and the data from the SCIRE collaborative study (which tracked SARS‐CoV‐2 variants in Italy) suggest that the Alfa variant (B.1.1.7 and B.1.1.7+E484K) was unequivocally preeminent from January to June 2021, while the Delta variant (B.1.617.2) became predominant from July to December 2021. Other minor circulating strains were the Beta variant (B.1.351) and the Gamma variant (P.1). 30 , 31 , 32 Vaccine efficacy against these variants was confirmed by several studies even if protective immunity rapidly declines over time. 33 , 34 Our study suggests that increasing vaccination coverage and implementing booster doses, in order to prevent infection, hospitalizations, serious illness, and death, is essential in a frail population such as cancer patients. High‐risk subjects may also benefit from additional mitigation measures that could reduce the risk of exposure. This suggestion could be extended to the general population in the global fight against COVID‐19. Additional studies are warranted in order to assess the clinical efficacy in cancer patients who received booster doses of the anti‐COVID‐19 vaccine. AUTHOR CONTRIBUTIONS Maria Silvia Cona: Conceptualization (equal); data curation (equal); project administration (equal); writing – original draft (equal); writing – review and editing (equal). Agostino Riva: Conceptualization (equal); funding acquisition (equal); methodology (equal); project administration (equal); resources (equal); supervision (equal); writing – review and editing (equal). Davide Dalu: Conceptualization (equal); data curation (equal); writing – original draft (equal); writing – review and editing (equal). Arianna Gabrieli: Data curation (equal); writing – review and editing (equal). Cinzia Fasola: Data curation (equal); writing – review and editing (equal). Giuseppe Lipari: Writing – review and editing (equal). Giacomo Pozza: Writing – review and editing (equal). Eliana Rulli: Formal analysis (equal); software (equal); supervision (equal); validation (equal); visualization (equal). Francesca Galli: Formal analysis (equal); software (equal); visualization (equal). Lorenzo Ruggieri: Data curation (equal); writing – original draft (equal); writing – review and editing (equal). Elsa Masedu: Data curation (equal). Gaia Parma: Data curation (equal); writing – original draft (equal). Davide Chizzoniti: Data curation (equal). Anna Gambaro: Investigation (equal). Sabrina Ferrario: Investigation (equal). Maria Antista: Writing – review and editing (equal). Matteo De Monte: Data curation (equal); investigation (equal). Maciej S. Tartowski: Writing – review and editing (equal). Nicla Maria La Verde: Conceptualization (equal); methodology (equal); project administration (equal); supervision (equal); writing – review and editing (equal). CONFLICT OF INTEREST STATEMENT N.L.V. reports grant from Eisai; speaker bureau from GSK; travel expenses for conference from Gentili, Celgene, and Pfizer; advisory role from Novartis and Celgene; advisory role, travel expenses for conference from Pfizer; advisory board from MSD, Roche, Novartis, Astrazeneca, and Daiichi Sanyo. D.D. reports receiving grants from Gentili, travel expenses from Roche, Gentili, and Eisai. M.S.C. has served on the advisory board from Daiichi Sanyo. There are no other personal or financial conflicts of interest to disclose. ETHICS STATEMENT The study protocol was approved by the Istituto Spallanzani Ethical Committee and AIFA (number 312 of the experimental registry 2020/2021) and conducted according to the principles of the Declaration of Helsinki. All the participants signed written informed consent before any study procedure. All subject data were anonymized as required by the Italian Data Protection Code (Legislative Decree 196/2003) and the general authorizations issued by the Italian Data Protection Authority. ACKNOWLEDGMENTS This project has received funding from the European Union's Horizon Europe Research and Innovation Actions under grant no. 101046041. The authors gratefully acknowledge the study patients. The authors also thank Joanna Landi for her technical assistance and the volunteers of “Salute Donna Onlus” for their collaboration. DATA AVAILABILITY STATEMENT The data generated in this study are available upon request from the corresponding author. ==== Refs REFERENCES 1 Cucinotta D , Vanelli M . WHO declares COVID‐19 a pandemic. Acta Biomed. 2020;91 :157‐160.32191675 2 https://www.who.int/director‐general/speeches/detail/who‐director‐general‐s‐opening‐remarks‐at‐the‐media‐briefing‐on‐covid‐19‐11‐march‐2020 visited in October 21, 2022 3 https://covid19.who.int/ Accessed October 21, 2022 4 Liang W , Guan W , Chen R , et al. Cancer patients in SARS‐CoV‐2 infection: a nationwide analysis in China. Lancet Oncol. 2020;21 (3 ):335‐337. doi:10.1016/S1470-2045(20)30096-6 32066541 5 Sharafeldin N , Bates B , Song Q , et al. Outcomes of COVID‐19 in patients with cancer: report from the national COVID cohort collaborative (N3C). J Clin Oncol. 2021;39 (20 ):2232‐2246. doi:10.1200/JCO.21.01074 34085538 6 Garassino MC , Whisenant JG , Huang LC , et al. COVID‐19 in patients with thoracic malignancies (TERAVOLT): first results of an international, registry‐based, cohort study. Lancet Oncol. 2020;21 (7 ):914‐922. doi:10.1016/S1470-2045(20)30314-4 32539942 7 Arayici ME , Kipcak N , Kayacik U , et al. Effects of SARS‐CoV‐2 infections in patients with cancer on mortality, ICU admission and incidence: a systematic review with meta‐analysis involving 709,908 participants and 31,732 cancer patients. J Cancer Res Clin Oncol. 2022;13 :1‐14. doi:10.1007/s00432-022-04191-y.Epub ahead of print. 8 Di Felice G , Visci G , Teglia F , Angelini M , Boffetta P . Effect of cancer on outcome of COVID‐19 patients: a systematic review and meta‐analysis of studies of unvaccinated patients. Elife. 2022;11 :e74634. doi:10.7554/eLife.74634 35171096 9 Riera R , Bagattini ÂM , Pacheco RL , Pachito DV , Roitberg F , Ilbawi A . Delays and disruptions in cancer health care due to COVID‐19 pandemic: systematic review. JCO Glob Oncol. 2021;7 :311‐323.33617304 10 Mentrasti G , Cantini L , Vici P , et al. Rising incidence of late stage breast cancer after COVID‐19 outbreak. Real‐world data from the Italian COVID‐DELAY study. Breast. 2022;65 :164‐171. doi:10.1016/j.breast.2022.08.007 35998429 11 Mentrasti G , Cantini L , Zichi C , et al. Alarming drop in early stage colorectal cancer diagnoses after COVID‐19 outbreak: a real‐world analysis from the Italian COVID‐DELAY study. Oncologist. 2022;27 (9 ):e723‐e730. doi:10.1093/oncolo/oyac129 35815922 12 Cantini L , Mentrasti G , Russo GL , et al. Evaluation of COVID‐19 impact on DELAYing diagnostic‐therapeutic pathways of lung cancer patients in Italy (COVID‐DELAY study): fewer cases and higher stages from a real‐world scenario. ESMO Open. 2022;7 (2 ):100406. Epub 2022 Feb 3. Erratum in: ESMO Open. 2022 Apr 1;7(2):100471. doi:10.1016/j.esmoop.2022.100406 35219245 13 Dalu D , Rota S , Cona MS , et al. A proposal of a "ready to use" COVID‐19 control strategy in an oncology ward: utopia or reality? Crit Rev Oncol Hematol. 2021;157 :103168. doi:10.1016/j.critrevonc.2020.103168 33254038 14 Di Noia V , Pimpinelli F , Renna D , et al. Immunogenicity and safety of COVID‐19 vaccine BNT162b2 for patients with solid cancer: a large cohort prospective study from a single institution. Clinical Cancer Research. 2021;27 (24 ):6815‐6823. doi:10.1158/1078-0432.CCR-21-2439 34583970 15 Addeo A , Shah PK , Bordry N , et al. Immunogenicity of SARS‐CoV‐2 messenger RNA vaccines in patients with cancer. Cancer Cell. 2021;39 (8 ):1091‐1098.e2. doi:10.1016/j.ccell.2021.06.009 34214473 16 La Verde N , Riva A , Cona MS , et al. Immunogenicity of two doses of BNT162b2 and mRNA‐1273 vaccines for solid cancer patients on treatment with or without a previous SARS‐CoV‐2 infection. Int J Cancer. 2022;152 (4 ):661‐671. doi:10.1002/ijc.34273 36056571 17 Wu JT , La J , Branch‐Elliman W , et al. Association of COVID‐19 vaccination with SARS‐CoV‐2 infection in patients with cancer: a US Nationwide veterans affairs study. JAMA Oncol. 2022;8 (2 ):281‐286. doi:10.1001/jamaoncol.2021.5771 34854921 18 Fendler A , de Vries EGE , GeurtsvanKessel CH , et al. COVID‐19 vaccines in patients with cancer: immunogenicity, efficacy and safety. Nat Rev Clin Oncol. 2022;19 (6 ):385‐401. doi:10.1038/s41571-022-00610-8 35277694 19 Thomas SJ , Perez JL , Lockhart SP , et al. Efficacy and safety of the BNT162b2 mRNA COVID‐19 vaccine in participants with a history of cancer: subgroup analysis of a global phase 3 randomized clinical trial. Vaccine. 2022;40 (10 ):1483‐1492. doi:10.1016/j.vaccine.2021.12.046 35131133 20 Heudel P , Favier B , Assaad S , Zrounba P , Blay JY . Reduced SARS‐CoV‐2 infection and death after two doses of COVID‐19 vaccines in a series of 1503 cancer patients. Ann Oncol. 2021;32 (11 ):1443‐1444. doi:10.1016/j.annonc.2021.07.012 34333128 21 Kuderer NM , Lyman GH . COVID‐19 vaccine effectiveness in patients with cancer: remaining vulnerabilities and uncertainties. Lancet Oncol. 2022;23 (6 ):693‐695. doi:10.1016/S1470-2045(22)00252-2 35617990 22 Peeters M , Verbruggen L , Teuwen L , et al. Reduced humoral immune response after BNT162b2 coronavirus disease 2019 messenger RNA vaccination in cancer patients under antineoplastic treatment. ESMO Open. 2021;6 (5 ):100274. doi:10.1016/j.esmoop.2021.100274 34597941 23 Lasagna A , Lilleri D , Agustoni F , et al. Analysis of the humoral and cellular immune response after a full course of BNT162b2 anti‐SARS‐CoV‐2 vaccine in cancer patients treated with PD‐1/PD‐L1 inhibitors with or without chemotherapy: an update after 6 months of follow‐up. ESMO Open. 2022;7 (1 ):100359. doi:10.1016/j.esmoop.2021.100359 34973510 24 Di Noia V , Pimpinelli F , Renna D , et al. Clinical characteristics limiting the durability of humoral response to BNT162b2 in patients with solid cancer. Ann Oncol. 2022;33 (3 ):350‐352. doi:10.1016/j.annonc.2021.11.015 34861377 25 Havers FP , Pham H , Taylor CA , et al. COVID‐19‐associated hospitalizations among vaccinated and unvaccinated adults 18 years or older in 13 US states, January 2021 to April 2022. JAMA Intern Med. 2022;182 (10 ):1071‐1081.36074486 26 Ligumsky H , Dor H , Etan T , et al. Wolf I; COVI3 study investigators. Immunogenicity and safety of BNT162b2 mRNA vaccine booster in actively treated patients with cancer. Lancet Oncol. 2022;23 (2 ):193‐195. doi:10.1016/S1470-2045(21)00715-4 Epub 2021 Dec 23.34953523 27 Robbiani DF , Gaebler C , Muecksch F , et al. Convergent antibody responses to SARS‐CoV‐2 in convalescent individuals. Nature. 2020;584 :437‐442. doi:10.1038/s41586-020-2456-9 32555388 28 Fendler A , STC S , Au L , et al. Adaptive immunity and neutralizing antibodies against SARS‐CoV‐2 variants of concern following vaccination in patients with cancer: the CAPTURE study. Nat Cancer. 2021;2 :1305‐1320. doi:10.1038/s43018-021-00274-w 35121899 29 Cona MS , Rulli E , Dalu D , et al. The emotional impact of the COVID‐19 outbreak on cancer outpatients and their caregivers: results of a survey conducted in the midst of the Italian pandemic. Support Care Cancer. 2022;30 (2 ):1115‐1125. doi:10.1007/s00520-021-06489-y 34432171 30 https://www.epicentro.iss.it/coronavirus/sars‐cov‐2‐monitoraggio‐varianti‐rapporti‐periodici. Accessed October 21, 2022 31 Lai A , Bergna A , Menzo S , et al. Circulating SARS‐CoV‐2 variants in Italy, October 2020‐March 2021. Virol J. 2021;18 (1 ):168. doi:10.1186/s12985-021-01638-5 34391446 32 Lai A , Bergna A , Ventura CD , et al. Epidemiological and clinical features of SARS‐CoV‐2 variants circulating between April–December 2021 in Italy. Viruses. 2022;14 :2508. doi:10.3390/v14112508 36423117 33 Fiolet T , Kherabi Y , MacDonald CJ , Ghosn J , Peiffer‐Smadja N . Comparing COVID‐19 vaccines for their characteristics, efficacy and effectiveness against SARS‐CoV‐2 and variants of concern: a narrative review. Clin Microbiol Infect. 2022;28 (2 ):202‐221. doi:10.1016/j.cmi.2021.10.005 34715347 34 Collier DA , De Marco A , IATM F , et al. Sensitivity of SARS‐CoV‐2 B.1.1.7 to mRNA vaccine‐elicited antibodies. Nature. 2021 May;593 (7857 ):136‐141. doi:10.1038/s41586-021-03412-7 33706364 35 Massarweh A , Eliakim‐Raz N , Stemmer A , et al. Evaluation of seropositivity following BNT162b2 messenger RNA vaccination for SARS‐CoV‐2 in patients undergoing treatment for cancer. JAMA Oncol. 2021;7 (8 ):1133‐1140. doi:10.1001/jamaoncol.2021.2155 34047765