Updated International Society of Geriatric Oncology COVID-19 working group recommendations on COVID-19 vaccination among older adults with cancer

Abstract

Two years after the declaration of the COVID-19 pandemic by the World Health Organization (WHO), its effects continue to have a negative social and health impact. Despite the implementation of global vaccination campaigns which have successfully reduced hospitalizations and mortality rates in many regions of the world, there are still many unresolved issues and challenges to tackle before the pandemic is over. While 65% of the world's population has received at least one dose of the COVID-19 vaccine, vaccination coverage is still very low in many regions of the world, particularly in low- and middle-income countries (LMIC) [[1]Our World in Data Coronavirus (COVID-19) Vaccinations.https://ourworldindata.org/covid-vaccinations?country=~MEXGoogle Scholar]. Older adults, particularly those who are unvaccinated and those with comorbidities such as cancer, continue to be at significant risk of increased morbidity and mortality when contracting COVID-19 [[2]Elkrief A. Hennessy C. Kuderer N.M. Rubinstein S.M. Wulff-Burchfield E. Rosovsky R.P. et al.Geriatric risk factors for serious COVID-19 outcomes among older adults with cancer: a cohort study from the COVID-19 and cancer consortium.Lancet Healthy Longev. 2022; 3: e143-e152https://doi.org/10.1016/s2666-7568(22)00009-5Abstract Full Text Full Text PDF PubMed Google Scholar]. While early in the pandemic significant changes in the administration of anticancer therapies (including omitting and delaying therapy) were undertaken, in many parts of the world cancer care delivery has returned to the same level as before COVID-19 [[3]Battisti N.M.L. Mislang A.R. Cooper L. O’Donovan A. Audisio R.A. Cheung K.L. et al.Adapting care for older cancer patients during the COVID-19 pandemic: Recommendations from the International Society of Geriatric Oncology (SIOG) COVID-19 Working Group.J Geriatric Oncol. 2020; 11: 1190-1198https://doi.org/10.1016/j.jgo.2020.07.008Abstract Full Text Full Text PDF PubMed Scopus (42) Google Scholar]. The emergence of the omicron variants of SARS-CoV-2, which show substantial resistance to vaccine-induced serum neutralizing activity, highlights the relevance of ongoing public health interventions, continued mass immunization, and booster campaigns targeting the most vulnerable members of society, including older adults with cancer [[4]Vanshylla K. Tober-Lau P. Gruell H. Munn F. Eggeling R. Pfeifer N. et al.Durability of omicron-neutralising serum activity after mRNA booster immunisation in older adults.Lancet Infect Dis. 2022; 22: 445-446https://doi.org/10.1016/S1473-3099(22)00135-9Abstract Full Text Full Text PDF PubMed Scopus (6) Google Scholar]. In 2021, the International Society of Geriatric Oncology (SIOG) published an initial set of recommendations regarding COVID-19 vaccinations among older adults with cancer [[5]Mislang A.R. Soto-Perez-de-Celis E. Russo C. Colloca G. Williams G.R. O’Hanlon S. et al.The SIOG COVID-19 working group recommendations on the rollout of COVID-19 vaccines among older adults with cancer.J Geriatr Oncol. 2021; 12: 848-850https://doi.org/10.1016/j.jgo.2021.03.003Abstract Full Text Full Text PDF PubMed Scopus (9) Google Scholar]. However, recent changes in the epidemiology of the disease and in data regarding COVID-19 vaccines require updated recommendations. As of April 2022, data for 34 COVID-19 vaccines have been successfully submitted for authorization by the WHO, 14 have been approved, and over 150 are currently under clinical development [[6]World Health Organization COVID-19 vaccine tracker and landscape.https://www.who.int/publications/m/item/draft-landscape-of-covid-19-candidate-vaccinesGoogle Scholar]. As vaccinations and vaccine boosters are becoming increasingly available in most regions of the world, those at higher risk of adverse outcomes including hospitalization and/or death should continue to be prioritized. Older people have been grossly underrepresented in randomized clinical trials (RCT) of the COVID-19 vaccine [[7]Helfand B.K.I. Webb M. Gartaganis S.L. Fuller L. Kwon C.S. Inouye S.K. The exclusion of older persons from vaccine and treatment trials for coronavirus disease 2019-missing the target.JAMA Intern Med. 2020; 180: 1546-1549https://doi.org/10.1001/jamainternmed.2020.5084Crossref PubMed Scopus (44) Google Scholar]. In the same way, patients with cancer, comorbidities, or those receiving immunosuppressive therapy have been excluded. The only published RCT including patients with cancer was the BNT162b2 Pfizer/BioNTech mRNA vaccine trial, which recently reported a subgroup analysis of the 3813 patients with a history of cancer (median age 64 years, range 16–91 years), showing an efficacy of 92–94%, with only four cases reported among the 1802 participants who received the vaccine compared with 71 among those who received placebo [[8]Thomas S.J. Perez J.L. Lockhart S.P. Hariharan S. Kitchin N. Bailey R. 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: 1483-1492https://doi.org/10.1016/j.vaccine.2021.12.046Crossref PubMed Scopus (5) Google Scholar]. This causes clinicians to make recommendations based on the risk-benefit ratio, on extrapolation of RCT data, on subgroup analyses, or on observational studies, particularly in the context of the emergence of novel variants. The efficacy of vaccines relies on an intact host response, which could be disrupted in people with myelosuppression due to cancer or its treatment, and in older adults (secondary to an age-related dysregulation and immune dysfunction commonly called immunosenescence), leading to potentially lower immunogenicity of vaccines in these population subgroups [[9]Crooke S.N. Ovsyannikova I.G. Poland G.A. Kennedy R.B. Immunosenescence and human vaccine immune responses.Immun Age. 2019; 16: 25https://doi.org/10.1186/s12979-019-0164-9Crossref PubMed Google Scholar]. A reduced magnitude and duration of immune responses among older adults after receiving mRNA and inactivated virus vaccines has also been reported, with reduced IgG levels, a lower proportion of specific memory B-cells, and a reduction in IL-2-producing T cells [[10]Collier D.A. Ferreira I.A.T.M. Kotagiri P. Datir P.R. Lim E.Y. Touizer E. et al.Age-related immune response heterogeneity to SARS-CoV-2 vaccine BNT162b2.Nature. 2021; 596: 417-422https://doi.org/10.1038/s41586-021-03739-1Crossref PubMed Scopus (181) Google Scholar]. Humoral responses and T cell activation have been found to be significantly lower among older adults, and to have a sharper decline over time, highlighting the relevance of providing booster doses for this population [10Collier D.A. Ferreira I.A.T.M. Kotagiri P. Datir P.R. Lim E.Y. Touizer E. et al.Age-related immune response heterogeneity to SARS-CoV-2 vaccine BNT162b2.Nature. 2021; 596: 417-422https://doi.org/10.1038/s41586-021-03739-1Crossref PubMed Scopus (181) Google Scholar, 11Brockman M.A. Mwimanzi F. Lapointe H.R. Sang Y. Agafitei O. Cheung P.K. et al.Reduced magnitude and durability of humoral immune responses to COVID-19 mRNA vaccines among older adults.J Infect Dis. 2021; 225: 1129-1140https://doi.org/10.1093/infdis/jiab592Crossref Scopus (15) Google Scholar, 12Bag Soytas R. Cengiz M. Islamoglu M.S. Borku Uysal B. Yavuzer S. Yavuzer H. Antibody responses to COVID-19 vaccines in older adults.J Med Virol. 2022; 94: 1650-1654https://doi.org/10.1002/jmv.27531Crossref PubMed Scopus (3) Google Scholar]. Likewise, patients with cancer seem more likely to develop a reduced immune response to COVID-19 vaccination. Vaccination effectiveness for preventing severe COVID-19 infections, although high, is lower among patients with cancer than among the general population, and even lower for those receiving active treatments and of advanced chronological age [[13]Embi P.J. Levy M.E. Naleway A.L. Patel P. Gaglani M. Natarajan K. et al.Effectiveness of 2-dose vaccination with mRNA COVID-19 vaccines against COVID-19-associated hospitalizations among immunocompromised adults - Nine States, January-September 2021.MMWR Morb Mortal Wkly Rep. 2021; 70: 1553-1559https://doi.org/10.15585/mmwr.mm7044e3Crossref PubMed Google Scholar,[14]Wu J.T.-Y. La J. Branch-Elliman W. Huhmann L.B. Han S.S. Parmigiani G. 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: 281-286https://doi.org/10.1001/jamaoncol.2021.5771Crossref PubMed Scopus (12) Google Scholar]. Real-world evidence shows that both patients aged ≥65 years and those with cancer have a higher risk of developing COVID-19 infections, and of adverse outcomes, despite vaccination [[15]Song Q. Bates B. Shao Y.R. Hsu F.C. Liu F. Madhira V. et al.Risk and outcome of breakthrough COVID-19 infections in vaccinated patients with cancer: real-world evidence from the national COVID cohort collaborative.J Clin Oncol. 2022 Mar 14; JCO2102419https://doi.org/10.1200/JCO.21.02419Crossref Scopus (11) Google Scholar]. Specifically, patients aged ≥65 with a diagnosis of cancer have an increased risk of adverse COVID-19-related outcomes (odds ratio [OR] 1.42, p = 0.01) than their younger counterparts [[15]Song Q. Bates B. Shao Y.R. Hsu F.C. Liu F. Madhira V. et al.Risk and outcome of breakthrough COVID-19 infections in vaccinated patients with cancer: real-world evidence from the national COVID cohort collaborative.J Clin Oncol. 2022 Mar 14; JCO2102419https://doi.org/10.1200/JCO.21.02419Crossref Scopus (11) Google Scholar]. Data from the United Kingdom shows that patients on moderate-to-high intensity chemotherapy are at increased risk of dying from COVID-19 despite being vaccinated (two doses) [[16]Hippisley-Cox J. Coupland C.A. Mehta N. Keogh R.H. Diaz-Ordaz K. Khunti K. et al.Risk prediction of COVID-19 related death and hospital admission in adults after covid-19 vaccination: National prospective cohort study.BMJ. 2021; 374n2244https://doi.org/10.1136/bmj.n2244Crossref Scopus (57) Google Scholar]. The exact timing of the vaccination during active chemo/immunotherapy does not seem to influence the efficacy of the vaccination significantly, except for patients undergoing stem cell-transplantation or receiving anti-CD20 therapies [[17]Thakkar A. Gonzalez-Lugo J.D. Goradia N. Gali R. Shapiro L.C. Pradhan K. et al.Seroconversion rates following COVID-19 vaccination among patients with cancer.Cancer Cell. 2021; 39: 1081-1090.e2https://doi.org/10.1016/j.ccell.2021.06.002Abstract Full Text Full Text PDF PubMed Scopus (143) Google Scholar]. Importantly, booster doses of COVID-19 vaccine seem to be effective at increasing antibody titres, as well as improving immune response to variants of concern among patients with cancer, and thus this should be a priority population in booster campaigns [[18]Naranbhai V. St. Denis K.J. Lam E.C. Ofoman O. Garcia-Beltran W.F. Mairena C.B. et al.Neutralization breadth of SARS-CoV-2 viral variants following primary series and booster SARS-CoV-2 vaccines in patients with cancer.Cancer Cell. 2022; 40: 103-108.e2https://doi.org/10.1016/j.ccell.2021.12.002Abstract Full Text Full Text PDF PubMed Scopus (11) Google Scholar,[19]Fendler A. Shepherd S.T.C. Au L. Wilkinson K.A. Wu M. Byrne F. 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: 1305-1320https://doi.org/10.1038/s43018-021-00274-wCrossref PubMed Scopus (35) Google Scholar]. The SIOG COVID-19 Working Group advocates for continued prioritization of older adults with cancer in vaccination campaigns and boosters to protect this vulnerable group from the adverse outcomes of COVID-19, even in the absence of robust data, following the recommendations included in Table 1 [[5]Mislang A.R. Soto-Perez-de-Celis E. Russo C. Colloca G. Williams G.R. O’Hanlon S. et al.The SIOG COVID-19 working group recommendations on the rollout of COVID-19 vaccines among older adults with cancer.J Geriatr Oncol. 2021; 12: 848-850https://doi.org/10.1016/j.jgo.2021.03.003Abstract Full Text Full Text PDF PubMed Scopus (9) Google Scholar].Table 1Updated SIOG COVID-19 Working Group recommendations for COVID-19 vaccinations among older patients with cancer.RecommendationRationaleA. For immediate actionPrioritize initial vaccination courses and vaccine boosters for individuals at disproportionate risk of death and other complications from COVID-19, including older patients with active or progressive cancer, or anticancer therapy at high risk for immunosuppression.Higher 30-day all-cause mortality from COVID-19 observed in patients with older age, comorbidities, active or progressive cancer [[20]Kuderer N.M. Choueiri T.K. Shah D.P. Shyr Y. Rubinstein S.M. Rivera D.R. et al.Clinical impact of COVID-19 on patients with cancer (CCC19): a cohort study.Lancet. 2020; 395: 1907-1918https://doi.org/10.1016/s0140-6736(20)31187-9Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar].Immune response to COVID-19 vaccines declines faster among older individuals and thus specific measures to boost vaccine responses in this population are warranted [[10]Collier D.A. Ferreira I.A.T.M. Kotagiri P. Datir P.R. Lim E.Y. Touizer E. et al.Age-related immune response heterogeneity to SARS-CoV-2 vaccine BNT162b2.Nature. 2021; 596: 417-422https://doi.org/10.1038/s41586-021-03739-1Crossref PubMed Scopus (181) Google Scholar,[11]Brockman M.A. Mwimanzi F. Lapointe H.R. Sang Y. Agafitei O. Cheung P.K. et al.Reduced magnitude and durability of humoral immune responses to COVID-19 mRNA vaccines among older adults.J Infect Dis. 2021; 225: 1129-1140https://doi.org/10.1093/infdis/jiab592Crossref Scopus (15) Google Scholar].Administering at least one booster dose seems to be effective in increasing immune response among patients with cancer. Data regarding subsequent booster doses is currently missing or very limited [[18]Naranbhai V. St. Denis K.J. Lam E.C. Ofoman O. Garcia-Beltran W.F. Mairena C.B. et al.Neutralization breadth of SARS-CoV-2 viral variants following primary series and booster SARS-CoV-2 vaccines in patients with cancer.Cancer Cell. 2022; 40: 103-108.e2https://doi.org/10.1016/j.ccell.2021.12.002Abstract Full Text Full Text PDF PubMed Scopus (11) Google Scholar,[19]Fendler A. Shepherd S.T.C. Au L. Wilkinson K.A. Wu M. Byrne F. 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: 1305-1320https://doi.org/10.1038/s43018-021-00274-wCrossref PubMed Scopus (35) Google Scholar,[21]Bar-On Y.M. Goldberg Y. Mandel M. Bodenheimer O. Amir O. Freedman L. et al.Protection by a Fourth Dose of BNT162b2 against Omicron in Israel.N Engl J Med. 2022; https://doi.org/10.1056/NEJMoa2201570Crossref Scopus (49) Google Scholar].Implement the use of regulated vaccines and vaccine boosters in areas with high community transmission and with a high prevalence of variants of concern as soon as possible and without interrupting active treatment.Except for patients receiving anti CD-20 antibodies or undergoing stem cell transplantation (for whom a delay of at least three months after treatment may be appropriate) [[22]National Comprehensive Cancer Network Recommendations of the NCCN COVID-19 vaccination advisory committee version 2.0 03/10/2021.https://www.nccn.org/covid-19/pdf/COVID-19_Vaccination_Guidance_V2.0.pdfGoogle Scholar], patients receiving anticancer therapies such as chemotherapy, targeted, endocrine therapy, or immunotherapy seem to be able to mount appropriate immune responses, particularly after boosters [[17]Thakkar A. Gonzalez-Lugo J.D. Goradia N. Gali R. Shapiro L.C. Pradhan K. et al.Seroconversion rates following COVID-19 vaccination among patients with cancer.Cancer Cell. 2021; 39: 1081-1090.e2https://doi.org/10.1016/j.ccell.2021.06.002Abstract Full Text Full Text PDF PubMed Scopus (143) Google Scholar].Persevere with community-based intervention strategies, such as physical distancing, hand hygiene, mask wearing, and use of personal protective equipment to mitigate transmission, even for patients and healthcare professionals that have already been vaccinated.Emerging COVID-19 variants, particularly omicron variants, are highly transmissible even among vaccinated individuals, and specifically among patients with cancer [[23]Araf Y. Akter F. Tang Y.D. Fatemi R. Parvez S.A. Zheng C. et al.Omicron variant of SARS-CoV-2: Genomics, transmissibility, and responses to current COVID-19 vaccines.J Med Virol. 2022; 94: 1825-1832https://doi.org/10.1002/jmv.27588Crossref PubMed Scopus (100) Google Scholar,[24]Pinato D.J. Aguilar-Company J. Ferrante D. Hanbury G. Bower M. Salazar R. et al.Outcomes of the SARS-CoV-2 omicron (B.1.1.529) variant outbreak among vaccinated and unvaccinated patients with cancer in Europe: results from the retrospective, multicentre, OnCovid registry study.Lancet Oncol. 2022 Jun 2; (S1470–2045(22)00273-X)https://doi.org/10.1016/S1470-2045(22)00273-XAbstract Full Text Full Text PDF PubMed Scopus (7) Google Scholar].The timing and level of measures to contain the virus, such as travel restrictions, facilities shutdowns, and social distancing have impacted the incidence and mortality from COVID-19 [[25]Thu T.P.B. Ngoc P.N.H. Hai N.M. Tuan L.A. Effect of the social distancing measures on the spread of COVID-19 in 10 highly infected countries.Sci Total Environ. 2020; 742140430https://doi.org/10.1016/j.scitotenv.2020.140430Crossref PubMed Scopus (113) Google Scholar].Facilitate the availability of vaccines and boosters for older adults with cancer living in LMIC by means of negotiation of fair prices and by equitable distribution of the vaccine supply through international collaborations and partnerships.COVID-19 vaccines have been disproportionately utilized in high-income regions of the world [[1]Our World in Data Coronavirus (COVID-19) Vaccinations.https://ourworldindata.org/covid-vaccinations?country=~MEXGoogle Scholar].Increasing access in LMIC is in line with WHO recommendations for Let's #ACTogether for #VaccinEquity and the United Nations COVAX program.Ensure equitable and timely access to primary vaccination for older people within community, local, or national level.Achieving high and equitable global coverage with a COVID-19 primary vaccination series remains the highest priority and is fundamental to reducing COVID-19–related morbidity and mortality [[26]Mbaeyi S. Oliver S.E. Collins J.P. Godfrey M. Goswami N.D. Hadler S.C. et al.The advisory committee on immunization practices’ interim recommendations for additional primary and booster doses of COVID-19 vaccines - United States, 2021.MMWR Morb Mortal Wkly Rep. 2021; 70: 1545-1552https://doi.org/10.15585/mmwr.mm7044e2Crossref PubMed Google Scholar].Prioritize older patients with cancer from socially and medically disadvantaged populations, including those with poor access to healthcare or from underrepresented racial/ethnic groups, in vaccination campaigns.Higher incidence and mortality from COVID-19 in racial/ethnic minorities likely related to underlying disparities in social determinants of health [[27]Moore J.T. Ricaldi J.N. Rose C.E. Fuld J. Parise M. Kang G.J. et al.Disparities in incidence of COVID-19 among underrepresented racial/ethnic groups in counties identified as hotspots during June 5–18, 2020–22 States, February–June 2020.MMWR Morb Mortal Wkly Rep. 2020; 69: 1122-1126https://doi.org/10.15585/mmwr.mm6933e1Crossref PubMed Scopus (0) Google Scholar].Governments, international organizations, and medical associations, including SIOG, should create and disseminate educational messaging and risk communication campaigns aimed at combating misinformation and convincing the public, older adults with cancer, and their caregivers of the value and safety of vaccination.COVID-19 vaccine hesitancy is a global phenomenon which is highly variable across countries, and which is related with lower education and awareness, as well as inefficient government efforts [[28]Shakeel C.S. Mujeeb A.A. Mirza M.S. Chaudhry B. Khan S.J. Global COVID-19 vaccine acceptance: A systematic review of associated social and behavioral factors.Vaccines. 2022; 10: 110Crossref Scopus (18) Google Scholar]. Tackling this hesitancy is necessary to increase vaccination rates.Ensure the availability of antiviral medications and monoclonal antibodies for non-hospitalized vaccinated older adults aged ≥65 with hematologic malignancies, for older adults with cancer aged ≥65 who have not been previously vaccinated, and for those aged ≥75 years regardless of vaccination status.Antiviral medications and monoclonal antibodies may decrease disease progression and hospitalization among ambulatory patients with COVID-19. Prioritization of their use is recommended by the National Institutes of Health [[29]COVID-19 Treatment Guidelines Panel. Coronavirus disease 2019 (COVID-19) treatment guidelines. National Institutes of Health. https://www.covid19treatmentguidelines.nih.gov/. Accessed April 15 2022.Google Scholar].We encourage our members to continue investigating the vaccines' long-term safety and efficacy in older adults with cancer (including booster shots), particularly in the emerging variants of concern.Populations included in phase III RCT were mostly younger individuals without comorbidities. “Real-world” evidence can further support the effectiveness COVID-19 vaccines among populations such as older adults with cancer, particularly with the emergence of novel, more transmissible, variants. “Real-world” evidence can also inform the incidence of COVID-19 infections after primary vaccination and support prioritizing the administration of booster doses in vulnerable populations [[2]Elkrief A. Hennessy C. Kuderer N.M. Rubinstein S.M. Wulff-Burchfield E. Rosovsky R.P. et al.Geriatric risk factors for serious COVID-19 outcomes among older adults with cancer: a cohort study from the COVID-19 and cancer consortium.Lancet Healthy Longev. 2022; 3: e143-e152https://doi.org/10.1016/s2666-7568(22)00009-5Abstract Full Text Full Text PDF PubMed Google Scholar].We encourage our members to prioritize investigations on the impact of previous COVID-19 infections, aging, physical activity, function, frailty, and various anticancer treatments on vaccine efficacy and adverse effects. Experts in geriatrics should be embedded in the planning of future studies regarding COVID-19 and cancer.Abbreviations: SIOG, International Society of Geriatric Oncology; LMIC, low- and middle-income counties; WHO, World Health Organization. Open table in a new tab Abbreviations: SIOG, International Society of Geriatric Oncology; LMIC, low- and middle-income counties; WHO, World Health Organization. Therefore, SIOG continues to stress the prioritization of initial vaccination and vaccine boosters among patients at higher risk of morbidity and mortality from COVID-19, specifically older adults with cancer, when implementing global and local vaccination plans. AM: Honoraria Janssen, MSD, Novartis. KPL: National Cancer Institute in the United States (R00CA237744), Wilmot Cancer Institute Research Fellowship Award. Receipt of consultation fees: Pfizer and Seattle Genetics; Receipt of honoraria: Pfizer. KLC: Consultancy: Roche. SML: National Cancer Institute Cancer Center Support Grant (P30CA008748). EB: Receipt of travel supports: Pfizer, Sandoz. Receipt of honoraria: Eli Lilly, Pfizer, Seagen. Receipt of consultation fees: Daiichi, Pfizer, Sandoz. RK: Speaker/ Advisory Board / Honoraria: AstraZeneca, Pfizer, MSD, BMS, Astellas, J&J, Eisai, Ipsen, Amgen, Merck. NMLB: Advisory board: Pfizer, Abbott, Sanofi; speaker fees: Abbovie, Pfizer, Roche, Sanofi; travel grants: Genomic Health, Pfizer, Lilly. MA: Honoraria from Pfizer. All authors contributed to the manuscript.