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Table of Contents
REVIEW ARTICLE
Year : 2021  |  Volume : 4  |  Issue : 3  |  Page : 505-515

Vaccination practices, efficacy, and safety in adults with cancer: A narrative review


Department of Medical Oncology, Tata Memorial Center, Homi Bhabha National Institute, Mumbai, Maharashtra, India

Date of Submission04-Jul-2021
Date of Decision07-Sep-2021
Date of Acceptance10-Sep-2021
Date of Web Publication08-Oct-2021

Correspondence Address:
Kumar Prabhash
Department of Medical Oncology, Tata Memorial Hospital, Parel, Mumbai - 400 012, Maharashtra
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/crst.crst_156_21

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  Abstract 


Patients with cancer are at a high risk of morbidity and mortality from infections, due to immune alterations resulting from the underlying malignancy as well as from therapy directed towards it. We aim to review the existing literature on the burden of vaccine-preventable disease, current practices and the efficacy and safety of these vaccines in patients with cancer. We performed a PubMed search for studies on the efficacy and safety of vaccines in patients with cancer, published in English, on or after 2011 to July 2021. Searches were also made in Embase, MEDLINE, Cochrane CENTRAL, and Google Scholar. Articles for which the full text was not available, non-human studies, and those that were not in English were excluded. We screened 92 studies, and excluded 49 as they were focused on children, articles about therapeutic cancer vaccines, and vaccination in healthy populations or patients with non-malignant conditions. Finally, 43 studies were included. Most studies have shown commonly administered vaccines to be safe, with some diminution of antibody response and efficacy but with overall benefit, including mortality benefit in some cases. The key point in the vaccination of patients with cancer was found to be appropriate timing, which according to most of the existing literature appears to be before the initiation of chemotherapy or in between cycles. There is however a dearth of good literature, opening up a new area for potential research.

Keywords: Cancer, COVID-19, immunization, influenza, pneumococcal, vaccine


How to cite this article:
Sarkar L, Goli VB, Menon N, Patil VM, Noronha V, Prabhash K. Vaccination practices, efficacy, and safety in adults with cancer: A narrative review. Cancer Res Stat Treat 2021;4:505-15

How to cite this URL:
Sarkar L, Goli VB, Menon N, Patil VM, Noronha V, Prabhash K. Vaccination practices, efficacy, and safety in adults with cancer: A narrative review. Cancer Res Stat Treat [serial online] 2021 [cited 2021 Dec 9];4:505-15. Available from: https://www.crstonline.com/text.asp?2021/4/3/505/327763




  Introduction Top


Patients with cancer are at a heightened risk of morbidity and mortality from serious infections, a significant proportion of which may be vaccine-preventable. Active cancer is a state of susceptibility both due to the altered immune response resulting from the disease itself, as well as from cancer-directed therapy such as chemotherapy, radiotherapy, and immunosuppressive treatments such as corticosteroids.[1] As these agents act to destroy rapidly proliferating tumor cells, they also have similar effects on other cells, such as white blood cells that form the backbone of the immune response mounted against infections.

There are concerns regarding the safety of vaccines in patients with cancer, particularly live vaccines. Live vaccines, when administered to immunocompromised hosts, can produce a clinical infection resulting from unchecked replication of the virus. Further, there is little to no data on the durability of the immune response induced by vaccines in patients with cancer, although it is generally recognized that immunogenicity is impaired in such patients.

Vaccination in patients with cancer is an often-overlooked component of management by clinicians as well as patients, who tend to prioritize the treatment of the primary malignancy. The objective of this review is to explore the burden of vaccine-preventable diseases in patients with cancer and the available literature on the use, safety, and efficacy of vaccines in this patient group. We additionally aim to provide an overview of the current vaccination practices among patients with cancer, to identify lacunae in our understanding and to uncover areas for further research.


  Methods Top


We used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines for the conduct and reporting of this review article. We included studies reporting data on the safety, efficacy, and uptake of vaccination in patients with cancer. We selected studies that were in English, and had been published on or after 2011 to July 2021. We searched in PubMed, with the search string: (((vaccine) AND ((pneumococcal) OR (influenza) OR (meningococcal) OR (hepatitis B) OR (diphtheria) OR (tetanus) OR (measles) OR (mumps) OR (rubella) OR (varicella) OR (COVID-19) OR (coronavirus) OR (SARS-CoV-2)) AND ((cancer) OR (malignancy)) AND (adults)). We applied the following filters: Full text, humans, English, cancer, adult: 19+ years, from January 1, 2011 to July 30, 2021, and article type: guideline, meta-analysis, systematic review, and randomized control trial. We also searched in EMBASE, MEDLINE, Cochrane CENTRAL, and Google Scholar. We excluded articles for which the full text was not available, non-human studies, and those that were not in English. The search strategy is outlined in [Figure 1].
Figure 1: The search strategy for the literature search for the review on vaccination in patients with cancer

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  General Principles Top


Modes of immunization can be divided into three broad categories, as follows:

  1. Inactivated vaccines - pneumococcus, influenza, tetanus, diphtheria, hepatitis B
  2. Live, attenuated vaccines - measles-mumps-rubella and varicella
  3. Passive immunizations - hepatitis B immunoglobulin.


Patients with cancer have several specific concerns with regard to vaccination. Besides the innate impairment of immunity in such patients, chemotherapy or radiotherapy may also result in inadequate antibody responses. The timing of vaccination is another point of concern, with the optimal period for administration of inactivated vaccines being at least 2 weeks prior to the start of chemotherapy or other immunosuppressive therapy.[1] For live attenuated vaccines, this gap should be extended to at least 4 weeks. The Center for Disease Control (CDC) and the Infectious Diseases Society of America (IDSA) recommend delaying immunization following the initiation of chemotherapy until at least 3 months after the discontinuation of the immunosuppressive therapy. For patients receiving anti–B-cell antibodies, this period should be extended to 6 months.[2]


  Pneumococcal Pneumonia Vaccination Top


Invasive pneumococcal disease can result in significant morbidity and mortality. The presence of an underlying malignancy is a well-recognized risk factor for invasive pneumococcal disease. Large-scale population-based studies have found patients with underlying hematological or solid organ malignancies to have a significantly increased incidence of this condition.[3]

Pneumococcal vaccines are of two types, the 13-valent conjugated vaccine (PCV13) and the 23-valent polysaccharide vaccine (PPSV23).

Despite older studies suggesting a poor antibody response to the PPSV23 in patients with hematologic malignancies, PPSV23 vaccination has been found to significantly lower the risk of hospitalization due to pneumonia.[4] Li et al. in 2020 published data on 2188 vaccinated and 2188 unvaccinated individuals with prostate cancer who had been followed for 7 years.[5] Those vaccinated had a lower incidence density, i.e., a lower number of new cases per number of person-years of observation than those who did not receive the vaccine. Vaccine recipients also had a 0.48 times lower risk of hospitalization related to pneumonia. PPSV23 vaccination has also been found to significantly lower the rates of hospital admission due to pneumonia in older patients with colorectal cancer (P = 0.40).[6]

In 2012, the United States Advisory Committee on Immunization Practices (ACIP) also included the PCV13 among their recommendations for high-risk adults over the age of 19 years; generalized malignancy was included as one such high-risk condition.[7] The PCV13 vaccine was compared to PPSV23 in 128 patients of chronic lymphocytic leukemia and was found to result in a better immune response in 10 of 12 serotypes 1 month following vaccination and in 5 of 12 serotypes 6 months after.[8]

The recommended mode of administration is as follows:

Pneumococcal vaccine naïve persons should first be vaccinated with PCV13, followed 8 weeks later by PPSV23. For immunocompromised patients, including patients with cancer, the second PPSV23 dose should be offered at least 5 years following the first dose of PPSV23.

For those already vaccinated with PPSV23, a PCV13 dose should be given at least 1 year after the initial dose. If further doses of PPSV23 are to be given, it should be with a gap of at least 8 weeks or at least 5 years after the last.

A crucial point to be noted in this context is the magnitude and durability of the response to immunization in such patients, in view of the impaired immune mechanisms seen in individuals with cancer.

Timing has unequivocally been seen to be one of the most significant factors impacting the response to pneumococcal vaccination. The optimum timing for PCV13 vaccination in patients receiving chemotherapy was studied in a prospective randomized controlled trial where 92 individuals with gastric and colorectal cancer were randomly assigned to receive the vaccine either 2 weeks prior to initiation or on day 1 of chemotherapy.[9] No significant difference was found between the two arms, and the antibody responses achieved were found to be adequate. Efficacy was impacted only in case of treatment initiation within 10 days of immunization – demonstrated by lower antibody levels among patients who had a gap of ≤10 days between immunization and chemotherapy compared to those who received the vaccine at longer intervals. After the completion of 3 months of therapy, no difference was seen in the antibody levels reached.

In general, the optimal time for administering the pneumococcal vaccine may be considered to be before the initiation of cancer treatment. Vaccination at diagnosis would allow the maximum time for attaining an antibody response. Immunization during cancer-directed therapy is not recommended. Antibody response remains impaired up to 6 months after the completion of treatment;[10] individuals who have not been vaccinated previously may be vaccinated 3 months after the cessation of therapy. A single reimmunization is recommended by the CDC for patients at highest risk, at a gap of at least 5 years between doses.


  Influenza Vaccination Top


Recent data suggest that influenza accounts for as many as 600,000 deaths per year. Although there is a lack of data on the disease burden in India, according to estimates over the last decade, over 100,000 cases and 8000 deaths due to influenza were reported in India with a case fatality rate of 7.5%.[11] The incidence of influenza hospitalizations was as high as 46.8/10,000 patients. As with other vaccines, the key questions for influenza vaccination in patients with cancer remain the role of protective antibodies in preventing or reducing the morbidity of infection and the ability of such patients to mount an adequate immune response.

There is little data on the immunogenicity of the influenza vaccine in patients with solid tumors; the majority of studies have been done in patients with hematologic malignancies. In general, the response seen in patients with solid tumors is better than that of patients with hematologic malignancies and may be similar to that of healthy controls.[12],[13] Patients receiving chemotherapy, however, may have an impaired response to immunization. It is unclear whether the impaired response is due to the immunosuppression resulting from chemotherapy or the immune dysregulation inherent to the underlying malignancy, as aggressive disease tends to warrant more aggressive treatment.

Anti-CD20 antibodies, in particular, the mainstay of therapy for various hematolymphoid malignancies, have been recognized to cause impaired immune responses. A 2011 study on the immunogenicity of the influenza A (H1N1) 2009 virus vaccine showed that of the 67 patients who were either on current therapy with rituximab or had received rituximab within the last 6 months, none developed adequate antibody levels.[14] This strongly suggests that rituximab-treated patients are unlikely to mount similar responses to influenza vaccination as compared to healthy persons.

As with other vaccines, timing is a crucial factor for influenza vaccination in patients with cancer. A study in patients with breast cancer who received the influenza vaccine while on the 5-fluorouracil, epirubicin, cyclophosphamide regimen found them to have significantly lower responses to influenza virus vaccination in comparison to healthy controls. Administering the vaccine early in the chemotherapy cycle, on day 4, was found to result in better responses than on day 16.[15] In another study, patients with breast and lung cancer were given the influenza vaccine on days 1 and 11 of a 3-week chemotherapy cycle.[16] Comparable immune responses were achieved with vaccination on day 1 or on day 11.

The CDC recommends annual vaccination for patients with cancer. Vaccination soon after an intensive chemotherapy regimen or hematopoietic stem cell transplant (HSCT) may fail to achieve appropriate antibody responses, and even at a later stage, efficacy is likely to be limited.[17] There are some data to suggest that immunization between the chemotherapy cycles may lead to higher seroconversion rates than vaccination given on day 1 of chemotherapy. Most recommendations are for administering the vaccine at least 7 days into a chemotherapy cycle and at least 3 months following HSCT.[3] Large, prospective studies are needed to assess the response to vaccination in patients with cancer and to help decide the optimum timing for vaccination in such patients.

There are a few strategies employed to increase the effectiveness of the influenza vaccine in immunocompromised patients. In a randomized study on 85 children and young adults (3–21 years) with cancer or human immunodeficiency virus (HIV), 2 doses of high-dose or of standard-dose trivalent influenza vaccine were administered. The high-dose vaccine contained a fourfold higher quantity of three antigens (H3N2, H2N1, and influenza B) as compared to the standard-dose vaccine. Immunogenicity was assessed by the hemagglutination inhibition (HAI) titer, which is the highest dilution of serum that prevents attachment of the virus to red blood cells, thus providing a measure of antibody levels in the sera. Patients with leukemia who received the high-dose vaccine had significantly higher HAI titers to the influenza B antigen, while those with solid tumors had significantly higher HAI titers to the H1 antigen in comparison to recipients of the standard-dose vaccine, implying a higher immunogenicity with the high-dose vaccine in these patient groups.[18]

Other strategies to enhance immunogenicity include the use of two-dose vaccine regimens. The VACANCE study evaluated the efficacy of and tolerance to two doses of AS03A-adjuvanted H1N1 virus vaccine in patients with cancer on active therapy.[19] This vaccine is an inactivated influenza A (H1N1) vaccine containing the H1N1 immunizing antigen in combination with the adjuvant AS03, which has immunostimulatory potential. The seroconversion rates after one and two doses of the vaccine were 44% and 73%, respectively. There are some data to suggest that the adjuvanted vaccine led to a decreased all-cause mortality and hospital admissions among patients; however, the numbers were too small to arrive at any definitive conclusions.

Further, increasing vaccination rates among healthcare workers has been found to decrease nosocomial influenza infection rates in patients with cancer.[20] Besides healthcare personnel, the CDC recommends influenza vaccination of household contacts (including children above the age of 6 months) and caregivers of people at higher risk of morbidity and mortality from influenza.[21]


  Tetanus and Diphtheria Vaccination Top


The majority of the evidence for tetanus and diphtheria vaccination in patients with cancer has been obtained from bone marrow transplant recipients. The antibody concentrations following the tetanus toxoid injection in patients who had formerly been treated for hematologic malignancies were found to be lower as compared to healthy age-matched controls.[22] This may be explained by either the type of malignancy or prior treatment with chemotherapy. In comparison to patients with myeloid malignancies, those with lymphoid malignancies were found to have significantly higher rates of seronegativity (P = 0.0003). Factors associated with impaired immunity to tetanus included advanced disease and the receipt of more aggressive chemotherapy prior to immunization.

The ACIP recommends tetanus and diphtheria toxoid immunization for patients with cancer at the same dose and schedule as for the general population.


  Hepatitis B Vaccination Top


There are very limited data on the use of the hepatitis B vaccine in adults with cancer. It is, however, well known that adults with immunocompromised states have an impaired ability to mount clinically relevant antibody responses to the hepatitis B vaccine. Such results may be extrapolated to patients with cancer as well. A study published in 2015 suggested that despite inadequate responses in patients with cancer, early or higher doses of the hepatitis B vaccine or administration of booster doses could protect against infection during or following chemotherapy.[23]


  Meningococcal Vaccination Top


Individuals with cancer should receive meningococcal vaccination in accordance with the ACIP recommendations as with individuals with complement deficiencies, asplenia – functional or anatomical, and HIV-positive adolescents. The vaccine should be administered either prior to the initiation of cytotoxic therapy or upon recovery of the immune system following therapy.[24] Patients who received splenic radiation at doses greater than 30 Gy are deemed to have functional asplenia and should also be offered meningococcal vaccination as per the recommendations for patients who have undergone splenectomy.


  Live Vaccines Top


Measles, mumps, and rubella vaccination

The measles, mumps, and rubella (MMR) vaccine is contraindicated in immunocompromised persons. The 2013 ACIP guidelines recommend that immunocompromised patients who have been exposed to measles, such as those on treatment for acute lymphoblastic leukemia till at least 6 months after the completion of therapy should receive 400 mg/kg of intravenous immune globulin.[25]

For patients with leukemia, the administration of the MMR vaccine is recommended at least 3 months following the conclusion of chemotherapy and 6 months following therapy with anti-B cell antibodies.[26] Post-transplant immunization with live attenuated vaccines can be given 24 months following transplantation to recipients of autologous or allogeneic HSCT after the cessation of immunosuppressive therapies.

Rabies vaccination

There exist no collated data on the safety of the rabies vaccine in patients with cancer; however, evidence suggests that it is generally safe in immunocompromised patients.[27] Hence, its safety in patients with cancer may be extrapolated. Interestingly, there have been reports of cancer regression following rabies vaccination, suggesting a potential role as an immune adjuvant to the current immunotherapeutic approaches (e.g. immune checkpoint inhibitors) in cancers such as glioblastoma and melanoma.

Varicella vaccination

Varicella vaccine is contraindicated in immunocompromised adults. Due to this reason, the best way to protect most individuals with cancer against the varicella virus is to vaccinate susceptible household contacts. Varicella vaccination in patients who have received chemotherapy should be avoided due to case reports of fatal occurrences of varicella infection resulting from vaccination in patients on or following chemotherapy or transplant. A study by Tseng et al. showed that older adults vaccinated against varicella-zoster would continue to remain protected in the event of later immunosuppression.[28] This highlights the need to vaccinate healthy individuals older than 60 years of age against varicella-zoster. Acceptable alternatives for immunocompromised at-risk persons on exposure to wild-type varicella virus include immune globulin prophylaxis alone or along with acyclovir.

Herpes Zoster vaccination

Recently, the adjuvanted recombinant zoster vaccine (Shingrix) was found to have acceptable safety and efficacy against herpes zoster infection in individuals with hematological malignancies.[29] Data on its use in patients with solid malignancies have also been published - the vaccine was immunogenic in such patients on chemotherapy.[30] The humoral and cell-mediated immune responses achieved were durable, persisting up to one year after vaccination.


  Vaccine Preventable Cancers Top


Human papillomavirus (HPV) and hepatitis B are key infections with the potential to trigger a carcinogenic process. The hepatitis B vaccine has been discussed above in the context of prevention of infection. It was also the first vaccine with the potential to prevent carcinogenesis, and after universal vaccination has led to reduced incidences of childhood hepatocellular carcinoma in Taiwan and other countries.[31]

The ACIP and the CDC recommend HPV vaccination in girls and boys aged 11 or 12 years. If this is not achieved, catch-up immunization may still be offered up to the age of 26 years.[32] Catch-up vaccination is the vaccination of individuals who have not been previously vaccinated or who have not completed the vaccine series. For immunocompromised patients as well, the ACIP recommends following the general vaccination schedule. As with other vaccines, the immune response may be weaker than that in immunocompetent adults.

There are little data on the risk of developing cervical cancer and other HPV-associated conditions among cancer survivors. With improved treatment options and an increased life expectancy among cancer survivors, the incidence of cervical cancer and other HPV-associated cancers may be expected to rise in this group. Hence, there is an important need for HPV vaccination in these individuals. The treating oncologist plays an important role in recommending the HPV vaccine to cancer survivors and providing them with adequate information allowing for vaccine decision-making.[33]


  COVID-19 Vaccination Top


The National Comprehensive Cancer Network (NCCN) recommends prioritizing the vaccination of patients with active cancer undergoing treatment, those scheduled for cancer-directed therapy, and those who have recently (<6 months) concluded treatment, except for those receiving only hormonal therapy.[34] Adverse prognosis in patients with cancer is linked to age ≥65 years, the presence of comorbidities, and sociodemographic factors such as poverty. The NCCN also specifically recommends that individuals on hematopoietic cell transplant (HCT) or cellular therapies such as chimeric antigen T-cell (CAR-T cell) therapy should delay vaccination for at least 3 months post-treatment to ensure maximal efficacy. Importantly, the NCCN also recommends that COVID-19 vaccination be prioritized over other vaccines that may be indicated in these patients.

Comprehensive data on vaccine safety and efficacy in patients with cancer or those on therapies directed toward cancer are still evolving. In a prospective, observational study published in June 2021, it was found that a single dose of the BNT162b2 (Pfizer) vaccine had poor efficacy in patients with cancer in comparison to healthy controls.[35] There was a significant rise in immunogenicity in patients with solid malignancies within 14 days of a booster dose at day 21. Thus, there is evidence to suggest that patients with cancer should be given priority for receiving their second dose early (day 21). The mRNA-1273 (Moderna COVID-19 vaccine) trial did not include any patients with cancer.[36] Only 0.5% of the patients in the Ad26.COV2.S (Janssen COVID-19 vaccine) phase III trial had cancer, and 0.2% had an immunocompromised state secondary to HCT.[37]

The Covaxin (manufactured by the Indian Council of Medical Research/Bharat Biotech) trial excluded patients receiving treatment with immunosuppressive or cytotoxic drugs or anticancer chemotherapy or radiotherapy within the preceding 36 months.[38] ChAdOx1 nCov-19 (AZD-1222 or Covishield) developed by AstraZeneca excluded patients with a history of primary malignancy, with the exception of cancers with a low risk of recurrence after curative treatment or metastasis (such as indolent prostate cancer) as per the investigator's judgment.[39]

The Interim CDC ACIP guidelines do not specifically mention patients with cancer, but they do advocate vaccinating immunocompromised patients in the absence of any contraindications.[40] Specific groups such as patients with chronic lymphocytic leukemia or on therapy with anti-CD20 monoclonal antibodies, Bruton tyrosine kinase inhibitors, or HCT or cellular therapies such as CAR-T cell therapy may experience a suboptimal response to vaccination. Such patients, in particular, should be counseled about the unknown safety and efficacy of the vaccine in their condition.

The American Society of Clinical Oncology and IDSA in December 2020 hosted a webinar with a panel discussion between infectious disease specialists and oncologists to guide the use of the COVID-19 vaccine in patients with cancer.[41] According to them, there was no evidence to suggest that these vaccines would not be safe for most of these patients, although there was a paucity of data. They suggested that patients with active or a prior history of cancer may be offered vaccination in the absence of any contraindication. Although immunosuppressed patients may experience a blunted response to the COVID-19 vaccine, they recognized that it may still help to reduce the risk and severity of COVID-19 infection.

The American Society for Hematology recommends vaccination between chemotherapy cycles. The vaccine may be administered at least 3 months after the conclusion of HCT or CAR-T cell therapy.[42] Patients planned for cytotoxic or B-cell-depleting therapies may be considered for vaccination prior to the initiation of treatment with a gap of at least 2 weeks to allow memory T-cell formation.

It is important to note that all these recommendations are speculative and are essentially expert opinions. There are no data at present to suggest that vaccination at 3 months (or any other interval) post-transplant or CAR-T-cell therapy would bolster clinically relevant immune responses against COVID-19. Ongoing graft-versus-host disease or continuing immunosuppression can further suppress an immune response. However, in the absence of data to the contrary and in view of the higher morbidity of COVID-19 infection in patients with cancer[43], the benefit of the doubt may be applied, and vaccination should be offered to such patients after counseling them sufficiently regarding the potential outcomes.


  Special Populations Top


Geriatric population

A retrospective study published in 2012 found that recently diagnosed adults with cancer have much lower rates of vaccination against influenza than other older adults, despite regular contact with healthcare services.[44] These individuals have heightened susceptibility to influenza because of compromised immune systems, but patients themselves as well as their treating clinicians may prioritize treatment of their cancer and overlook the importance of vaccination. Furthermore, the type of provider - primary care provider versus specialized oncologist, influenced the administration of preventive care services.

The International Society of Geriatric Oncology COVID-19 Working Group recommends the prioritization of COVID-19 vaccination in older adults with cancer.[45] For patients on chemotherapy, vaccination should be at the time of bone marrow function recovery or a few days prior to the next cycle, to minimize side effects and enhance efficacy. They have also highlighted the importance of future research into the impact of aging on vaccine efficacy and safety.

Transplant recipients

In general, vaccine effectiveness is measured by antibody titers. For allogeneic HSCT patients, it is necessary to develop markers to measure humoral and cellular response and immune memory.[46] Recommendations for vaccination at 24 months' post-transplant are not based on robust evidence, and studies are needed on the optimal timing and the number of doses of the vaccine to be administered in HCT recipients.[47] As vaccines generally lead to suboptimal responses in allogeneic HSCT recipients and live attenuated vaccines are contraindicated, it is essential to vaccinate their relatives and close contacts.

Following transplantation, antibody levels to several bacteria and viruses decline in the initial few months, including Streptococcus pneumonia,[48] Hemophilus influenzae type b[49] and measles. Response to most vaccines is curtailed in HSCT recipients during the 1st month or year.[50] The IDSA recommends considering HSCT recipients as never-vaccinated.[1] There is a need for complete immunization programs with recommendations based on the age and country of residence taking local epidemiology into account. The 7th European Conference on Infections in Leukemia provided a set of guidelines in 2017 based on existing evidence.[51] A summary of the current recommendations is listed in [Table 1].
Table 1: Recommendations for vaccination post-hematopoietic stem cell transplant

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  Vaccine Uptake in Patients with Cancer Top


There are scant data available on the uptake of vaccines in patients with cancer. A study done on patients with conditions leading to secondary immune deficiencies, including autoimmune diseases, solid organ transplant, and therapy for hematological malignancies found immunization rates to be 49% and 59% for invasive pneumococcal disease and influenza, respectively.[52] Vaccine uptake is dependent upon a number of factors, including:

  • Religious[53]
  • Social[54]
  • Philosophical
  • Lack of trust in vaccine providers[55]
  • Fear of vaccines and adverse outcomes following immunization.[56]


The uptake of COVID-19 vaccination has grown to be of paramount importance in recent times, particularly among immunocompromised populations such as patients with cancer. In a study on ambulatory inpatients in 4 French cancer centers, 53.7% were ready for immediate vaccination, 29.7% stated their hesitation but that they were likely to change their mind eventually, and 16.6% refused vaccination.[57] Another study on Mexican women with breast cancer had a 34% vaccine refusal rate.[58] A study done among 435 patients at the Tata Memorial Hospital in Mumbai, India, showed a 59.4% rate of vaccine hesitancy.[59]

The uptake of vaccination in Indian patients with cancer has been found to range from 20% to 29%,[59],[60] leaving large room for improvement. Communication is perhaps the most effective means to improve vaccine uptake.[61] Educational campaigns for patients and physicians about the effectiveness, safety, and advantages of vaccines, educating and reinforcing first-contact family physicians, and enhancing coordination between family physicians and oncologists would aid in improving coverage of vaccines.

[Table 2] enumerates the results of various studies describing the uptake of vaccination in patients with cancer.
Table 2: Vaccination uptake in patients with cancer

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  Recommendations Top


Although the principal existing guidelines on immunization provide some light on this key, often-neglected component of oncological practice, there is still a need for more comprehensive guidelines, specific to the region, patient group, and associated conditions.

[Table 3] summarizes the available guidelines in this context.
Table 3: Summary of principal guidelines on vaccination of patients with cancer

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Finally, based on the data reviewed, certain practical recommendations may be made on the use of vaccines in patients with cancer, as shown in [Table 4].
Table 4: Practical overview of vaccines in patients with cancer

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  Conclusions Top


The need for large, well-designed studies on the efficacy, safety, and optimal administration of vaccines in patients with cancer is still largely unmet, and most recommendations are opinion-driven and based on individual physician experience and anecdotal data. The available evidence is largely from higher income Western nations, with little data on Indian patients. In general, the penetration of vaccination among patients with cancer in most studies is low, and may be assumed to be similar for India even though no comprehensive data exist for the same. It is important to prioritize and consolidate the role of routine vaccination as a part of the standard of care for patients with cancer and to establish safety, efficacy, and appropriate timing of each of them through further studies.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.[66]



 
  References Top

1.
Rubin LG, Levin MJ, Ljungman P, Davies EG, Avery R, Tomblyn M, et al. 2013 IDSA clinical practice guideline for vaccination of the immunocompromised host. Clin Infect Dis 2014;58:309-18.  Back to cited text no. 1
    
2.
Berglund A, Willén L, Grödeberg L, Skattum L, Hagberg H, Pauksens K. The response to vaccination against influenza A (H1N1) 2009, seasonal influenza and Streptococcus pneumoniae in adult outpatients with ongoing treatment for cancer with and without rituximab. Acta Oncol 2014;53:1212-20.  Back to cited text no. 2
    
3.
Bitterman R, Eliakim-Raz N, Vinograd I, Zalmanovici Trestioreanu A, Leibovici L, Paul M. Influenza vaccines in immunosuppressed adults with cancer. Cochrane Database Syst Rev 2018;2:CD008983.  Back to cited text no. 3
    
4.
Chiou WY, Lee MS, Hung SK, Lin HY, Lo YC, Hsu FC, et al. Effectiveness of 23-valent pneumococcal polysaccharide vaccine on elderly long-term cancer survivors: A population-based propensity score matched cohort study. BMJ Open 2018;8:e019364.  Back to cited text no. 4
    
5.
Li CY, Chen LC, Lin HY, Lee MS, Hung SK, Lai CL, et al. Impact of 23-valent pneumococcal polysaccharide vaccination on the frequency of pneumonia-related hospitalization and survival in elderly patients with prostate cancer: A seven-year nationwide matched cohort study. Cancer 2020;127:124-36.  Back to cited text no. 5
    
6.
Chiou WY, Hung SK, Lin HY, Chen LC, Hsu FC, Tsai SJ, et al. Effectiveness of 23-valent pneumococcal polysaccharide vaccine on elderly patients with colorectal cancer: A population-based propensity score-matched cohort study. Medicine (Baltimore) 2019;98:e18380.  Back to cited text no. 6
    
7.
Centers for Disease Control and Prevention (CDC). Use of 13-valent pneumococcal conjugate vaccine and 23-valent pneumococcal polysaccharide vaccine for adults with immunocompromising conditions: Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep 2012;61:816-9.  Back to cited text no. 7
    
8.
Svensson T, Kättström M, Hammarlund Y, Roth D, Andersson PO, Svensson M, et al. Pneumococcal conjugate vaccine triggers a better immune response than pneumococcal polysaccharide vaccine in patients with chronic lymphocytic leukemia A randomized study by the Swedish CLL group. Vaccine 2018;36:3701-7.  Back to cited text no. 8
    
9.
Choi W, Kim JG, Beom SH, Hwang JE, Shim HJ, Cho SH, et al. Immunogenicity and optimal timing of 13-valent pneumococcal conjugate vaccination during adjuvant chemotherapy in gastric and colorectal cancer: A randomized controlled trial. Cancer Res Treat 2020;52:246-53.  Back to cited text no. 9
    
10.
Rendo M, Sgrignoli R, Dela Cruz W. EPR20-073: The effects of chemotherapy on the efficacy of pneumococcal vaccination using pneumococcal vaccine antibody titers as correlate. J Natl Compr Canc Netw 2020;18:EPR20-073.  Back to cited text no. 10
    
11.
Dhar R, Ghoshal AG, Guleria R, Sharma S, Kulkarni T, Swarnakar R, et al. Clinical practice guidelines 2019: Indian consensus-based recommendations on influenza vaccination in adults. Lung India 2020;37:S4-18.  Back to cited text no. 11
    
12.
Anderson H, Petrie K, Berrisford C, Charlett A, Thatcher N, Zambon M. Seroconversion after influenza vaccination in patients with lung cancer. Br J Cancer 1999;80:219-20.  Back to cited text no. 12
    
13.
Sanada Y, Yakushijin K, Nomura T, Chayahara N, Toyoda M, Minami Y, et al. A prospective study on the efficacy of two-dose influenza vaccinations in cancer patients receiving chemotherapy. Jpn J Clin Oncol 2016;46:448-52.  Back to cited text no. 13
    
14.
Yri OE, Torfoss D, Hungnes O, Tierens A, Waalen K, Nordøy T, et al. Rituximab blocks protective serologic response to influenza A (H1N1) 2009 vaccination in lymphoma patients during or within 6 months after treatment. Blood 2011;118:6769-71.  Back to cited text no. 14
    
15.
Meerveld-Eggink A, de Weerdt O, van der Velden AM, Los M, van der Velden AW, Stouthard JM, et al. Response to influenza virus vaccination during chemotherapy in patients with breast cancer. Ann Oncol 2011;22:2031-5.  Back to cited text no. 15
    
16.
Keam B, Kim MK, Choi Y, Choi SJ, Choe PG, Lee KH, et al. Optimal timing of influenza vaccination during 3-week cytotoxic chemotherapy cycles. Cancer 2017;123:841-8.  Back to cited text no. 16
    
17.
Engelhard D, Mohty B, de la Camara R, Cordonnier C, Ljungman P. European guidelines for prevention and management of influenza in hematopoietic stem cell transplantation and leukemia patients: Summary of ECIL-4 (2011), on behalf of ECIL, a joint venture of EBMT, EORTC, ICHS, and ELN. Transpl Infect Dis 2013;15:219-32.  Back to cited text no. 17
    
18.
Hakim H, Allison KJ, Van de Velde LA, Tang L, Sun Y, Flynn PM, et al. Immunogenicity and safety of high-dose trivalent inactivated influenza vaccine compared to standard-dose vaccine in children and young adults with cancer or HIV infection. Vaccine 2016;34:3141-8.  Back to cited text no. 18
    
19.
Rousseau B, Loulergue P, Mir O, Krivine A, Kotti S, Viel E, et al. Immunogenicity and safety of the influenza A H1N1v 2009 vaccine in cancer patients treated with cytotoxic chemotherapy and/or targeted therapy: The VACANCE study. Ann Oncol 2012;23:450-7.  Back to cited text no. 19
    
20.
Frenzel E, Chemaly RF, Ariza-Heredia E, Jiang Y, Shah DP, Thomas G, et al. Association of increased influenza vaccination in health care workers with a reduction in nosocomial influenza infections in cancer patients. Am J Infect Control 2016;44:1016-21.  Back to cited text no. 20
    
21.
Grohskopf LA, Alyanak E, Broder KR, Blanton LH, Fry AM, Jernigan DB, et al. Prevention and control of seasonal influenza with vaccines: recommendations of the advisory committee on immunization practices – United States, 2020–21 Influenza season. MMWR Recomm Rep 2020;69:1-24.  Back to cited text no. 21
    
22.
Hammarström V, Pauksen K, Björkstrand B, Simonsson B, Oberg G, Ljungman P. Tetanus immunity in autologous bone marrow and blood stem cell transplant recipients. Bone Marrow Transplant 1998;22:67-71.  Back to cited text no. 22
    
23.
Sodhi JS, Raja W, Zargar SA, Showkat A, Parveen S, Nisar S, et al. The efficacy of accelerated, multiple, double-dose hepatitis B vaccine against hepatitis B virus infection in cancer patients receiving chemotherapy. Indian J Gastroenterol 2015;34:372-9.  Back to cited text no. 23
    
24.
Centers for Disease Control and Prevention (CDC). Recommendation of the advisory committee on immunization practices (ACIP) for use of quadrivalent meningococcal conjugate vaccine (MenACWY-D) among children aged 9 through 23 months at increased risk for invasive meningococcal disease. MMWR Morb Mortal Wkly Rep 2011;60:1391-2.  Back to cited text no. 24
    
25.
McLean HQ, Fiebelkorn AP, Temte JL, Wallace GS; Centers for Disease Control and Prevention. Prevention of measles, rubella, congenital rubella syndrome, and mumps, 2013: Summary recommendations of the advisory committee on immunization practices (ACIP). MMWR Recomm Rep 2013;62:1-34.  Back to cited text no. 25
    
26.
Pergam SA, Englund JA, Kamboj M, Gans HA, Young JH, Hill JA, et al. Preventing measles in immunosuppressed cancer and hematopoietic cell transplantation patients: A position statement by the American society for transplantation and cellular therapy. Biol Blood Marrow Transplant 2019;25:e321-30.  Back to cited text no. 26
    
27.
Altinoz MA, Guloksuz S, Elmaci I. Rabies virus vaccine as an immune adjuvant against cancers and glioblastoma: New studies may resurrect a neglected potential. Clin Transl Oncol 2017;19:785-92.  Back to cited text no. 27
    
28.
Tseng HF, Tartof S, Harpaz R, Luo Y, Sy LS, Hetcher RC, et al. Vaccination against zoster remains effective in older adults who later undergo chemotherapy. Clin Infect Dis 2014;59:913-9.  Back to cited text no. 28
    
29.
Dagnew AF, Ilhan O, Lee WS, Woszczyk D, Kwak JY, Bowcock S, et al. Immunogenicity and safety of the adjuvanted recombinant zoster vaccine in adults with haematological malignancies: A phase 3, randomised, clinical trial and post-hoc efficacy analysis. Lancet Infect Dis 2019;19:988-1000.  Back to cited text no. 29
    
30.
Vink P, Delgado Mingorance I, Maximiano Alonso C, Rubio-Viqueira B, Jung KH, Rodriguez Moreno JF, et al. Immunogenicity and safety of the adjuvanted recombinant zoster vaccine in patients with solid tumors, vaccinated before or during chemotherapy: A randomized trial. Cancer 2019;125:1301-12.  Back to cited text no. 30
    
31.
Kao JH. Hepatitis B vaccination and prevention of hepatocellular carcinoma. Best Pract Res Clin Gastroenterol 2015;29:907-17.  Back to cited text no. 31
    
32.
Markowitz LE, Dunne EF, Saraiya M, Chesson HW, Curtis CR, Gee J, et al. Human papillomavirus vaccination: Recommendations of the advisory committee on immunization practices (ACIP). MMWR Recomm Rep 2014;63:1-30.  Back to cited text no. 32
    
33.
Waters AR, Mann K, Vaca Lopez PL, Kepka D, Wu YP, Kirchhoff AC. HPV vaccine experiences and preferences among young adult cancer survivors and caregivers of childhood cancer survivors. J Cancer Educ 2021;10.1007/s13187-021-01992-6. Epub ahead of print.  Back to cited text no. 33
    
34.
National Comprehensive Cancer Network (NCCN). Cancer and COVID-19 Vaccination Version 3.0. Available from: https://www.nccn.org/docs/default-source/covid-19/2021_covid-19_vaccination_guidance_v3-0.pdf?sfvrsn=b483da2b_60. [Last accessed on 2021 Jul 11].  Back to cited text no. 34
    
35.
Monin L, Laing AG, Muñoz-Ruiz M, McKenzie DR, Del Molino Del Barrio I, Alaguthurai T, et al. Safety and immunogenicity of one versus two doses of the COVID-19 vaccine BNT162b2 for patients with cancer: Interim analysis of a prospective observational study. Lancet Oncol 2021;22:765-78.  Back to cited text no. 35
    
36.
Baden LR, El Sahly HM, Essink B, Kotloff K, Frey S, Novak R, et al. Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine. N Engl J Med 2021;384:403-16.  Back to cited text no. 36
    
37.
Janssen Biotech, Inc. COVID-19 Vaccine Ad26.COV2.S VRBPAC Briefing Document. FDA Briefing Document. Janssen Ad26.COV2.S Vaccine for the Prevention of COVID-19. Available from: https://www.fda.gov/media/146217/download. [Last accessed on 2021 Jul 11].  Back to cited text no. 37
    
38.
Ella R, Reddy S, Jogdand H, Sarangi V, Ganneru B, Prasad S, et al. Safety and immunogenicity of an inactivated SARS-CoV-2 vaccine, BBV152: Interim results from a double-blind, randomised, multicentre, phase 2 trial, and 3-month follow-up of a double-blind, randomised phase 1 trial. Lancet Infect Dis 2021;21:950-61.  Back to cited text no. 38
    
39.
Folegatti PM, Ewer KJ, Aley PK, Angus B, Becker S, Belij-Rammerstorfer S, et al. Safety and immunogenicity of the ChAdOx1 nCoV-19 vaccine against SARS-CoV-2: A preliminary report of a phase 1/2, single-blind, randomised controlled trial. Lancet 2020;396:467-78.  Back to cited text no. 39
    
40.
Available from: https://www.cdc.gov/vaccines/covid-19/downloads/summary-interim-clinical-considerations.pdf. [Last accessed on 2021 Jul 11].  Back to cited text no. 40
    
41.
American Society of Clinical Oncology (ASCO). COVID-19 Vaccines and Patients with Cancer. Available from: https://www.asco.org/asco-coronavirus-resources/covid-19-patient-care-information/covid-19-vaccine-patients-cancer. [Last accessed on 2021 Jul 11].  Back to cited text no. 41
    
42.
American Society of Hematology. ASH-ASTCT COVID-19 Vaccination for HCT and CAR T Cell Recipients: Frequently Asked Questions (Version 3.0). Available from: https://www.hematology.org/covid-19/ash-astct-covid-19-vaccination-for-hct-and-car-t-cell-recipients. [Last accessed on 2021 Jul 11].  Back to cited text no. 42
    
43.
Shrivastava SR, Shrivastava PS. Impact of the COVID-19 pandemic on patients with cancer and cancer survivors: A narrative review. Cancer Res Stat Treat 2021;4:315-20.  Back to cited text no. 43
  [Full text]  
44.
Locher JL, Rucks AC, Spencer SA, Pettaway GJ, Kilgore ML. Influenza immunization in older adults with and without cancer. J Am Geriatr Soc 2012;60:2099-103.  Back to cited text no. 44
    
45.
Mislang AR, Soto-Perez-de-Celis E, Russo C, Colloca G, Williams GR, 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;12:848-50.  Back to cited text no. 45
    
46.
Conrad A, Alcazer V, Valour F, Ader F; Lyon HEMINF Study Group. Vaccination post-allogeneic hematopoietic stem cell transplantation: What is feasible? Expert Rev Vaccines 2018;17:299-309.  Back to cited text no. 46
    
47.
Kennedy LB, Li Z, Savani BN, Ljungman P. Measuring immune response to commonly used vaccinations in adult recipients of allogeneic hematopoietic cell transplantation. Biol Blood Marrow Transplant 2017;23:1614-21.  Back to cited text no. 47
    
48.
Winston DJ, Ho WG, Schiffman G, Champlin RE, Feig SA, Gale RP. Pneumococcal vaccination of recipients of bone marrow transplants. Arch Intern Med 1983;143:1735-7.  Back to cited text no. 48
    
49.
Meerveld-Eggink A, van der Velden AM, Ossenkoppele GJ, van de Loosdrecht AA, Biesma DH, Rijkers GT. Antibody response to polysaccharide conjugate vaccines after nonmyeloablative allogeneic stem cell transplantation. Biol Blood Marrow Transplant 2009;15:1523-30.  Back to cited text no. 49
    
50.
Ljungman P, Cordonnier C, Einsele H, Englund J, Machado CM, Storek J, et al. Vaccination of hematopoietic cell transplant recipients. Bone Marrow Transplant 2009;44:521-6.  Back to cited text no. 50
    
51.
Cordonnier C, Einarsdottir S, Cesaro S, Di Blasi R, Mikulska M, Rieger C, et al. Vaccination of haemopoietic stem cell transplant recipients: Guidelines of the 2017 European conference on infections in leukaemia (ECIL 7). Lancet Infect Dis 2019;19:e200-12.  Back to cited text no. 51
    
52.
Loubet P, Kernéis S, Groh M, Loulergue P, Blanche P, Verger P, et al. Attitude, knowledge and factors associated with influenza and pneumococcal vaccine uptake in a large cohort of patients with secondary immune deficiency. Vaccine 2015;33:3703-8.  Back to cited text no. 52
    
53.
Pelčić G, Karačić S, Mikirtichan GL, Kubar OI, Leavitt FJ, Cheng-Tek Tai M, et al. Religious exception for vaccination or religious excuses for avoiding vaccination. Croat Med J 2016;57:516-21.  Back to cited text no. 53
    
54.
Shankar S, Dutta T. Understanding the Role and Impact of Gender in the Use of Immunization Services; Report of a study conducted in Jaipur, Rajasthan, India: PATH India; 2010.  Back to cited text no. 54
    
55.
Larson HJ, Clarke RM, Jarrett C, Eckersberger E, Levine Z, Schulz WS, et al. Measuring trust in vaccination: A systematic review. Hum Vaccin Immunother 2018;14:1599-609.  Back to cited text no. 55
    
56.
Goldstein S, MacDonald NE, Guirguis S. Health communication and vaccine hesitancy. Vaccine 2015;33:4212-4.  Back to cited text no. 56
    
57.
Barrière J, Gal J, Hoch B, Cassuto O, Leysalle A, Chamorey E, et al. Acceptance of SARS-CoV-2 vaccination among French patients with cancer: A cross-sectional survey. Ann Oncol 2021;32:673-4.  Back to cited text no. 57
    
58.
Villarreal-Garza C, Vaca-Cartagena BF, Becerril-Gaitan A, Ferrigno AS, Mesa-Chavez F, Platas A, et al. Attitudes and factors associated with COVID-19 vaccine hesitancy among patients with breast cancer. JAMA Oncol 2021;7:1242-4.  Back to cited text no. 58
    
59.
Noronha V, Abraham G, Bondili SK, Rajpurohit A, Menon RP, Gattani S, et al. COVID-19 vaccine uptake and vaccine hesitancy in Indian patients with cancer: A questionnaire-based survey. Cancer Res Stat Treat 2021;4:211-8.  Back to cited text no. 59
  [Full text]  
60.
Batra U, Nathany S, Bansal N, Sharma M. COVID-19 vaccination status in Indian patients with cancer: An observational study. Cancer Res Stat Treat 2021;4:219-23.  Back to cited text no. 60
  [Full text]  
61.
Monier A, Puyade M, Hernanz MP, Bouchaert P, Leleu X, Tourani JM, et al. Observational study of vaccination in cancer patients: How can vaccine coverage be improved? Med Mal Infect 2020;50:263-8.  Back to cited text no. 61
    
62.
Meidani M, Rostami M, Dehghani F. Why coverage of influenza vaccine is not enough in patients receiving chemotherapy? Int J Prev Med 2011;2:186-7.  Back to cited text no. 62
    
63.
Chin-Yee BH, Monkman K, Hussain Z, Minuk LA. Attitudes toward vaccination for pandemic H1N1 and seasonal influenza in patients with hematologic malignancies. J Support Oncol 2011;9:156-60.  Back to cited text no. 63
    
64.
Urun Y, Akbulut H, Demirkazik A, Cay Senler F, Utkan G, Onur H, et al. Perception about influenza and pneumococcal vaccines and vaccination coverage among patients with malignancies and their family members. J BUON 2013;18:511-5.  Back to cited text no. 64
    
65.
Kroger A, Bahta L, Hunter P. General Best Practice Guidelines for Immunization. Best Practices Guidance of the Advisory Committee on Immunization Practices (ACIP). Available from: https://www.cdc.gov/vaccines/hcp/acip-recs/general-recs/index.html. [Last accessed on 2021 Jul 11].  Back to cited text no. 65
    
66.
National Comprehensive Cancer Network. Prevention and Treatment of Cancer-Related Infections (Version 1.2021). Available from: https://www.nccn.org/professionals/physician_gls/pdf/infections.pdf. [Last accessed on 2021 Jul 11].  Back to cited text no. 66
    


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Abstract
Introduction
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Pneumococcal Pne...
Influenza Vaccin...
Tetanus and Diph...
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Meningococcal Va...
Live Vaccines
Vaccine Preventa...
COVID-19 Vaccination
Special Populations
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