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The SIOG COVID-19 working group recommendations on the rollout of COVID-19 vaccines among older adults with cancer

Published:March 05, 2021DOI:https://doi.org/10.1016/j.jgo.2021.03.003

      Keywords

      The COVID-19 pandemic continues to negatively impact our society. Older adults are at increased risk of morbidity and mortality. People who are frail, living in residential care facility, and/or with comorbidities, including cancer are disproportionately disadvantaged. To reduce the risk of infection among older adults with cancer, several anticancer therapies have been prioritized, delayed, de-escalated, or omitted based on clinical need (
      • 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.
      ). However, public health interventions remain critical to mitigate transmission and minimize adverse outcomes. Of these, mass immunization is perhaps a more effective preventive health measure and potentially a key exit strategy from this crisis.

      1. Considerations on the role of COVID-19 vaccines in older patients with cancer

      To date, data on eight COVID-19 vaccines have been successfully submitted for authorization by the World Health Organization (
      • Organization WH
      Status of COVID-19 Vaccines within WHO EUL/PQ evaluation process 2021.
      ), five vaccines have reported results on efficacy and/or safety (Table 1), and over 50 are at various stages of development. As vaccines are made available to the general population, their rollout should be prioritized for those at higher risk of adverse outcomes including hospitalization and/or death. Older individuals are traditionally excluded from or underrepresented in clinical trials, and the same holds true for COVID-19 vaccine studies (
      • 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.
      ). Similarly, patients with cancer, comorbidities, or immunosuppression have been excluded. Therefore, clinicians are expected to make recommendations based on the risk-benefit ratio and extrapolation of trial data to the real world until more information becomes available.
      Table 1Summary of the published results on COVID-19 Vaccines and efficacy in older people (in alphabetical order).
      VaccineNDesignTypeMain inclusion criteriaMain exclusion criteriaDose intervalEfficacyOlder adults inclusion and vaccine safety
      AstraZeneca

      AZD1222 (
      • Ramasamy M.N.
      • Minassian A.M.
      • Ewer K.J.
      • Flaxman A.L.
      • Folegatti P.M.
      • Owens D.R.
      • et al.
      Safety and immunogenicity of ChAdOx1 nCoV-19 vaccine administered in a prime-boost regimen in young and old adults (COV002): a single-blind, randomised, controlled, phase 2/3 trial.
      ,
      • Voysey M.
      • Clemens S.A.C.
      • Madhi S.A.
      • Weckx L.Y.
      • Folegatti P.M.
      • Aley P.K.
      • et al.
      Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK.
      )
      11,636Single blindChimpanzee adenovirus vectored vaccineAge ≥ 18 yearsSevere or uncontrolled medical comorbidities

      Participants aged ≥65 years with a Dalhousie Clinical Frailty Score of ≥4
      LD (2·2 × 1010 virus particles) or SD (3·5–6·5 × 1010 virus particles)

      x2

      28 days apart
      70.4%≥70 years (9.5%)

      In phase II component <70 (n = 79) vs. ≥70 (n = 49) years:

      Similar antibody response across all age groups

      Fewer reactogenicity events

      Localized AEs:

      82% vs. 61%

      Systemic AEs:

      82% vs. 65%
      Gam-COVID-Vac (Sputnik V) (
      • Logunov D.Y.
      • Dolzhikova I.V.
      • Shcheblyakov D.V.
      • Tukhvatulin A.I.
      • Zubkova O.V.
      • Dzharullaeva A.S.
      • et al.
      Safety and efficacy of an rAd26 and rAd5 vector-based heterologous prime-boost COVID-19 vaccine: an interim analysis of a randomised controlled phase 3 trial in Russia.
      )
      19,866Double blindrecombinant replication-deficient adenovirusAge ≥ 18 yearsImmunosuppression1 × 1011

      viral particles x 2, 21 days apart
      91.6%

      >60: 91.8%
      >60 years (10.8%)
      Janssen Ad26.COV2·S (
      • Sadoff J.
      • Le Gars M.
      • Shukarev G.
      • Heerwegh D.
      • Truyers C.
      • de Groot A.M.
      • et al.
      Interim results of a phase 1-2a trial of Ad26.COV2.S Covid-19 vaccine.
      )
      805Single blindModified adenovirusHealthy adults of 2 age cohorts

      1a: 18–55 years

      3: ≥65 years
      LD: (5 × 1010

      viral particles) or HD: (1 × 1011 viral particles) in single vs. 2 doses, 56 days apart
      >90%≥65 years (50%)

      Cohort 1a vs. 3

      Lower Immune response

      LD: 100% vs. 91%

      HD: 100% vs. 94%

      Lower incidence of AEs

      Localized AEs

      LD: 64% vs.41%

      HD: 65% vs.84%

      Systemic AEs

      LD: 78% vs. 42%

      HD: 46% vs. 55%
      Moderna mRNA-1273 (
      • Baden L.R.
      • El Sahly H.M.
      • Essink B.
      • Kotloff K.
      • Frey S.
      • Novak R.
      • et al.
      Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine.
      )
      30,420Double blindmRNAAge ≥ 18 years

      At high risk of COVID-19 infection by location or comorbidities
      Immunosuppression100μg x2 28 days apart94.1%

      <64: 95.6%

      ≥65: 86.4%
      >65 years (25%)

      Less common AEs in ≥65 (89%) vs. 18–64 (93%) years
      Pfizer BioNTech BNT162b2 (
      • Polack F.P.
      • Thomas S.J.
      • Kitchin N.
      • Absalon J.
      • Gurtman A.
      • Lockhart S.
      • et al.
      Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine.
      )
      43,548Double blindmRNAAge ≥ 16

      Healthy or stable chronic medical conditions
      Immunosuppression30 μg x2

      21 days apart
      95%>65 years (21%)

      Lower reactogenicity events in >55 years (2.8%) vs. 16–55 years (4.6%)
      LD: low dose; HD: high dose; SD: standard dose; AE: adverse events
      The efficacy of vaccines relies on an intact host response, which could be disrupted in people with myelosuppression due to cancer or its treatment. Age-related dysregulation and immune dysfunction, called immunosenescence, could potentially result in lower immunogenicity of vaccines in older adults (
      • Crooke S.N.
      • Ovsyannikova I.G.
      • Poland G.A.
      • Kennedy R.B.
      Immunosenescence and human vaccine immune responses.
      ). Physical exercise may augment vaccine-specific antibody responses; however, activities are limited by the imposed counter-pandemic measures. An adjuvanted vaccine may be used to overcome immunosenescence, as shown in the AZD1222 trial (
      • Ramasamy M.N.
      • Minassian A.M.
      • Ewer K.J.
      • Flaxman A.L.
      • Folegatti P.M.
      • Owens D.R.
      • et al.
      Safety and immunogenicity of ChAdOx1 nCoV-19 vaccine administered in a prime-boost regimen in young and old adults (COV002): a single-blind, randomised, controlled, phase 2/3 trial.
      ).
      Variability in the relationship between neutralizing- and binding-antibody titres in older adults was seen in the Ad26.COV2·S trial (
      • Sadoff J.
      • Le Gars M.
      • Shukarev G.
      • Heerwegh D.
      • Truyers C.
      • de Groot A.M.
      • et al.
      Interim results of a phase 1-2a trial of Ad26.COV2.S Covid-19 vaccine.
      ). Nevertheless, vaccine efficacy appears to be consistent in older subgroups with a trend for lower reactogenicity (Table 1). Notably, these findings are all based on short-term analyses, where the long-term efficacy is still unclear. Also, these studies did not include frailty measures nor large groups of older individuals, which limit the characterization of those recruited. Longer follow-up from vaccine trials will provide insight into the impact of vaccination on COVID-19 transmissibility, asymptomatic infections, or emerging mutant strains. The role of anticancer treatments, age, frailty and functional status on vaccine efficacy also needs to be investigated. Despite these caveats, the International Society of Geriatric Oncology (SIOG) COVID-19 Working Group advocates for a call to action to prioritize older adults with cancer in the vaccine rollout to protect this vulnerable group from the adverse outcomes of COVID-19, even in the absence of robust data.
      Tabled 1
      RecommendationRationale
      A. For immediate action
       Prioritize the rollout of vaccines to 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 immunosuppressionHigher 30-day all-cause mortality observed in patients with older age, comorbidities, active or progressive cancer (
      • 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.
      ).
       Implement the use of regulated vaccines at the earliest opportunity, especially in areas with high community transmission

      • For older patients receiving active anticancer therapy - if possible, schedule vaccination at the time of bone marrow function recovery and a few days before the next cycle to maximize its efficacy and minimize the impact of potential side effects on ongoing anticancer treatments.
      No specific data available on COVID-19 vaccine. Data extrapolated from experiences with influenza vaccine (
      • Vollaard A.
      • Schreuder I.
      • Slok-Raijmakers L.
      • Opstelten W.
      • Rimmelzwaan G.
      • Gelderblom H.
      Influenza vaccination in adult patients with solid tumours treated with chemotherapy.
      ). Recommendations from the UK Chemotherapy Board and Public Health England “Green Book” on Immunization Against Infectious Disease.

      The efficacy and timing on patients on immunosuppressive therapy still needs to be established.
       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 vaccinatedLimited evidence exists on the impact of vaccines on COVID-19 transmission.

      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 (
      • 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.
      ).
       Facilitate the availability of vaccines for older adults with cancer living in low and middle-income countries by means of negotiation of fair prices and by equitable distribution of the vaccine supply through international collaborations and partnerships.In line with WHO recommendations for Let's #ACTogether for #VaccinEquity and the United Nations COVAX program.
       Ensure equitable and timely access to vaccines in older people within community, local, or national level.
       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 (
      • 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.
      ).
       Create and disseminate educational messaging and risk communication campaigns aimed at convincing older adults with cancer and their caregivers of the value and safety of vaccinationAvoid “fake news”, misinformation, and minimize confusion from several media platforms by disseminating accurate information that is readily available/accessible to a wider audience.
       Foster collaboration with advocacy groups to dispel simplistic and populist statements suggesting that “access to vaccines should be prioritized based on the capacity to contribute to economy”, as these stigmatize aging people as a burden, thereby compromising ethics and health equityAdvocacy, community engagement, and cross-sectoral collaborations are key strategies to COVID-19 response (
      • Schiavo R.
      Advocacy, community engagement and cross-sectoral collaborations as key strategies during COVID-19 response and beyond.
      ).
      B. For subsequent action
       Investigate the vaccines' long-term safety, seroconversion, and seroprotection rates in older adults with cancerPopulations included in phase III randomized controlled trials were mostly younger individuals without comorbidities. “Real-world” evidence can further support the effectiveness COVID-19 vaccines among other populations such as older adults and patients with cancer.
       Prioritize investigations on the impact of aging, reduction in physical activities, function, frailty, and anticancer treatments on vaccine efficacy and adverse effects
      Therefore, SIOG joins the call of other international organizations for prioritizing patients at higher risk of morbidity and mortality from COVID-19, specifically older adults with cancer, when implementing global and local vaccination plans.

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