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. Author manuscript; available in PMC: 2023 Jan 25.
Published in final edited form as: Clin J Oncol Nurs. 2022 Jul 25;26(4):367–373. doi: 10.1188/22.CJON.367-373

COVID-19 Vaccines and Immunosuppressed Patients With Cancer: Critical Considerations

Naomi Cazeau 1, Meighan Palazzo 1, Malvi Savani 1, Rachna Shroff 1
PMCID: PMC9713690  NIHMSID: NIHMS1834518  PMID: 35939727

Abstract

Background:

Patients with cancer are highly vulnerable to COVID-19 and its most harmful effects due to immunosuppression from their disease and treatments. Emerging data has illuminated the impact of cancer and related treatments on patients’ response to COVID-19 vaccines. This paper reviews the unique considerations regarding COVID-19 vaccines for patients with cancer.

Objectives:

This paper aims to provide foundational knowledge on cancer and related treatment’s impact on humoral responses to the COVID-19 vaccine, vaccine scheduling for the immunosuppressed, and nursing considerations for vaccine administration for patients with cancer.

Methods:

Current research on immune responses to COVID-19 vaccines among immunosuppressed patients with hematologic and solid tumor malignancies are summarized along with CDC recommendations for vaccination of the immunosuppressed, and a review of related nursing considerations.

Findings:

Emerging literature on the humoral responses of patients with cancer to the COVID-19 vaccines are helping to guide vaccination planning for this special population. Nursing knowledge of the critical considerations for patients with cancer receiving COVID-19 vaccination is integral to the provision of optimal clinical oncology care amid a pandemic.

Keywords: COVID-19, vaccination, immunosuppression, hematology, solid tumor

Patients with cancer are at greater risk for contracting the SARS-CoV-2 virus, twice as likely to be hospitalized with COVID-19 infection, and three times more likely to die from it (Bakouny et al., 2020; Wang et al., 2021). Among the factors related to poor COVID-19 outcomes among patients with cancer is the immunosuppression many develop due to their disease and treatments (Bakouny et al., 2020; Chavez-MacGregor et al., 2022). The current FDA-approved COVID vaccines have demonstrated safety and efficacy at reducing COVID-related deaths in the general population and have largely been viewed as our society’s key to returning to normalcy. However, patients with cancer on active treatment were not included in the original studies of the vaccines (Elkrief et al., 2021). While the vaccines offer a pathway to society’s recovery from the pandemic, there are special considerations for patients with cancer, particularly those that are immunosuppressed. This paper reviews special considerations for patients with cancer receiving the COVID-19 vaccines as well as related patient teaching and clinical monitoring. The information included herein is current as of April 10, 2022. Given the evolving nature of the pandemic and related vaccine recommendations, Figure 1 provides additional resources where the latest guidelines can be found.

Figure 1.

Figure 1.

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Additional Resources

COVID-19 Vaccines

In the United States, there are currently two FDA-approved mRNA vaccines against COVID-19 (Pfizer-BioNTech and Moderna). The Johnson & Johnson (Janssen) vector vaccine has FDA authorization for emergency use (EUA) and is approved as for use as a heterologous booster following full vaccination with either mRNA vaccine.

mRNA vaccines:

these vaccines contain mRNA from the SARS-CoV-2 virus, created in a laboratory, that teach our cells how to make a piece of the spike protein that is present on the surface of the virus (Centers for Disease Control and Prevention [CDC],2022). The mRNA is destroyed by our cells after they make copies of the spike protein (CDC, 2022). The spike protein triggers an immune response that produces antibodies against the virus and builds T- and B-lymphocytes that will remember how to fight the SARS-CoV-2 virus if we become infected (CDC, 2022).

Vector vaccines:

these vaccines contain a modified version of a harmless virus that is different from the virus that causes COVID-19. This modified virus is known as a “vector virus” that carries spike protein DNA material from the virus that causes COVID-19 into our cells. (CDC, 2022). Once the viral vector is inside our cells, the genetic material instructs our cells to make the spike protein unique to the SARS-CoV-2 virus (CDC, 2022). The spike protein induces our bodies to produce T and B-lymphocytes that will remember how to fight the virus if we become infected (CDC, 2022).

Seroconversion, or the transition from COVID-19 vaccination to the development of serum antibodies, has been measured via antibody titers and serum SARS-CoV-2 neutralizing antibody levels (Pang et al., 2021; Ryding, 2021). While there has yet to be established antibody levels associated with durable vaccine response, higher antibody levels are generally considered to be associated with more durable immunity (Avivi et al., 2021).

For the general population, full vaccination with the Pfizer-BioNTech vaccine includes 2 intramuscular dose injections, given 3 weeks apart. The Moderna vaccine is administered as 2 intramuscular dose injections given 4 weeks apart. The Janssen vaccine includes 1 intramuscular injection (CDC, 2022). A booster dose of either mRNA vaccine may be given 5 months following full vaccination for those 12 years or older (Pfizer-BioNTech) or 18 years or older (Moderna) (CDC, 2022). Individuals receiving primary vaccination with the Janssen vaccine may be boosted at least 2 months following their initial dose (CDC, 2022).

COVID Vaccination in Immunosuppressed Patients

Immunosuppressed patients make up approximately 3% of the adult population in the United States and are defined as those with suppressed humoral or cellular immunity resulting from health conditions or medications (Embi et al., 2021). These patients are not only at increased risk for severe COVID-19 infection, extended hospitalization, intensive care admission, and mortality compared to the general population (Mehrabi Nejad et al, 2022), they also may not acquire the same level of protection from COVID-19 vaccination as do immunocompetent adults (Embi et al., 2021). Therefore, the CDC currently recommends a modified vaccine schedule for patients with moderate to severe immunocompromise (see Table 1), with a preference for mRNA vaccination in anyone over 18 due to risk of serious adverse effects with Johnson and Johnson vector vaccination.

Table 1.

COVID-19 Vaccine Schedule for Moderate to Severely Immunocompromised

Vaccine product Age group Primary vaccine doses Interval between 1st and 2nd dose Interval between 2nd and 3rd dose Interval between primary series and booster Interval between 1st and 2nd booster
Pfizer-BioNTech ≥ 12 years 3 3 weeks ≥ 4 weeks ≥ 12 weeks ≥ 4 months
Moderna ≥18 years 3 ≥ 4 weeks
Janssen ≥18 years 2** ≥ 28 days N/A ≥ 8 weeks ≥ 4 months ***
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**

Second vaccine dose must be mRNA (CDC, 2022).

***

mRNA only for second booster dose (CDC, 2022).

Source: Centers for Disease Control

CDC COVID vaccination recommendations for this group include the following:

People ages 12 years and older who are moderately or severely immunocompromised:

Patients may receive a total of 5 doses of COVID vaccination consisting of a primary series of 3 doses of an mRNA COVID-19 vaccine, and up to 2 booster doses of an mRNA COVID-19 vaccine. The Pfizer-BioNTech COVID-19 vaccine 2nd dose is given 21 days after the first dose, the 3rd dose is given 28 days after the second dose, an initial booster is given at least 3 months after the third dose. Moderate or severely immunocompromised patients over 12 years old may also receive a second booster of the Pfizer-BioNTech vaccine no less than 4 months after their first booster. The Moderna COVID-19 vaccine 2nd dose is given 28 days after the first dose, the 3rd dose is given 28 days after the second dose, an initial booster is given at least 3 months after the third dose, and patients over 18 may receive a second booster of the Moderna vaccine at least 4 months after their first booster (CDC, 2022).

People ages 18 years and older who are moderately or severely immunocompromised and received the 1 dose Johnson & Johnson’s Janssen COVID-19 vaccine:

Patients should receive a second dose of either Pfizer-BioNTech or Moderna COVID-19 vaccine (mRNA COVID-19 vaccines) given at least 28 days after the first dose of Janssen, followed by a booster of mRNA vaccination at least 2 months after the second dose. Patients 12 and over may also receive a 2nd booster of mRNA vaccine no less than 4 months after their first booster (CDC, 2022).

The CDC defines moderate to severe immune compromise as any patient (1) who has been receiving active cancer treatment for tumors or cancers of the blood (2) received an organ transplant and are taking medicine to suppress the immune system (3) received a stem cell transplant within the last 2 years or are taking medicine to suppress the immune system (4) moderate or severe primary immunodeficiency (such as DiGeorge syndrome, Wiskott-Aldrich syndrome) (5) advanced or untreated HIV infection (6) or on active treatment with high-dose corticosteroids or other drugs that may suppress their immune response (See Figure 2, CDC, 2022).

Research has shown patients with certain cancers undergoing specific treatments may have diminished immune responses to the vaccines, which may have implications for their level of protection (Elkrief et al., 2021). Below is an overview of current knowledge related to vaccine response in hematologic and solid tumor malignancies.

Hematologic Malignancies and COVID-19 Vaccines

Patients with multiple myeloma have compromised humoral and cellular immunity due to their plasma cell disorder, hypogammaglobulinemia, and therapies (Chung et al., 2021), and are at great risk for severe illness from infection with COVID-19 and breakthrough infections after vaccination (Gavriatopoulou et al., 2022; Stampfer et al., 2021). However, they have shown increased variability in immune response to the COVID-19 mRNA vaccines (Aleman et al., 2021). While patients with multiple myeloma generally respond to vaccination their response may be attenuated by their age (older patients showing lower response), disease status (lower response among patients with poorly controlled disease), decreased polyclonal globulin levels, lower lymphocyte counts, and disease-directed treatment (Avivi et al., 2021; Chung et al., 2021). Patients treated with anti B-cell maturation antigen (anti-BCMA) or anti-CD38 antibodies have been shown to have significantly diminished responses to the COVID-19 vaccine while those treated with immunomodulatory agents tend to maintain relatively intact immune responses to vaccination (Chung et al., 2021; Stampfer et al., 2021). In a study by Chung et al. (2021) comparing immune response among 551 vaccinated patients with hematological malignancies (N=221 with multiple myeloma) and healthy controls (N=69), patients treated with immunomodulatory agents showed median antibody titer levels of 198.8 (range: 36.85–624.5) artificial units per milliliter (AU/ml) post-vaccination at 1 month, and 2,397 AU/ml (range: 798.1–8,816) at 3 months. Patients treated with anti-CD38 antibodies had median antibody levels of 12.3 AU/ml (range: 1.7–56.7) at 1 month and 318 AU/ml (range: 50.1–1,594) at 3 months post-vaccination (Chung et al., 2021). Patients treated with anti-BCMA antibodies had median antibody titers of 9.6 AU/ml (range: 9.6–9.6) at 1 month and 36.4 AU/ml (range: 9.4–78.7) at 3months post-vaccination (Chung et al., 2021). These findings compare with healthy adults in the Chung et al. (2021) study who had median titer levels of 886.2 AU/ml (range: 502.3–2,240) at 1 month and 7,720 AU/ml (range: 3,885–9,746) at 3 months post-vaccination.

Despite some patients having a lower immune response to vaccination, vaccination and booster dosing is still recommended for all patients with multiple myeloma (Avivi et al., 2021; Gavriatopoulou et al., 2022). Data suggests patients with multiple myeloma may respond better to the mRNA-1273 (Moderna) vaccine as compared with BNT16b2 (Pfizer-BioNTech) (Avivi et al., 2021; Stampfer et al., 2021).

Among patients with lymphoma, defects in immune effector cells and disease-directed therapies may lead to suboptimal immune response to vaccines (Gavriatopoulou et al., 2021). Treatment with B-cell-directed therapies can adversely affect the production of antibodies in response to COVID-19 vaccination due to B-cell depletion and/or disruption of the B-cell receptor signaling pathway (Ghione et al., 2021). For instance, treatment with anti-CD20 antibodies, a common treatment for patients with lymphoma, reduces the response to COVID-19 vaccines particularly among patients vaccinated less than 12 months following anti-CD20 antibody treatment (Ghione et al., 2021; Gurion et al., 2021). Among the anti-CD20 antibodies, Gurion et al. (2021) found that patients treated with Obinutuzumab had lower vaccine response rates compared with Rituximab. Ibrutinib, which blocks B-cell receptor signaling in both malignant and normal B-cells, may also impair the humoral response to vaccination (Gavriatopoulou et al., 2021). As with multiple myeloma, active disease is also a significant predictor of poor serologic response to the BNT162b2 vaccine, possibly related to the effect of chemotherapy and corticosteroids on T-cell functionality which is necessary for the development of memory B- and plasma cells (Gurion et al., 2021; Herishanu et al., 2022). These nascent research findings underscore the importance of protective precautions (i.e., masks, social distancing) as well as vaccine booster dosing among this immunosuppressed population (Herishanu et al., 2022).

There is limited data currently available on COVID-19 vaccine response among patients with myeloid malignancies. Mori et al. (2022) completed a small study comparing the humoral response at 3 months post vaccination with mRNA-based vaccines among 69 patients with acute myeloid leukemia (AML; N =46) or myelodysplastic syndrome (MDS; N= 23) and healthy controls (N= 43). They found no significant difference in seroconversion rates between their patients with myeloid malignancies and healthy controls (94.7% and 100% respectively). However, patients with MDS had significantly lower antibody levels compared with AML patients (576 U/ml [range: 158.3–1708.8]; p= <.01) and healthy controls (1079 U/ml [range: 661.−1526]; p= <.0001). AML patients undergoing treatment had lower antibody levels compared with AML patients off therapy (92.2 U/ml [range: 37.5–216.3] vs. 1630 U/ml [range: 661 – 1526]; p= <.0001) (Mori et al., 2022).

Patients who have undergone COVID-19 vaccination prior to hematopoietic cell transplantation (HCT) or chimeric antigen receptor T cell (CAR-T) therapy are at high risk of losing their immunity. The timing of vaccination relative to HCT has been shown to influence vaccination response. A study by Huang et al. (2022) showed antibody responses to mRNA vaccines among allogeneic HCT recipients were significantly lower for those vaccinated within 1-year post-transplant compared to patients vaccinated over a year following HCT. Treatment with immunosuppressive medications (i.e., treatment or prevention of graft vs. host disease) can exacerbate this effect (Leclerc et al., 2022). Therefore, the CDC recommends revaccination with the full mRNA COVID vaccine series for immunosuppressed patients, regardless of pre-HCT or CAR-T vaccination history, which can be considered as early as 3 months post therapy (CDC, 2022).

Solid Tumor Malignancies and COVID-19 Vaccines

Patients with solid malignancies tend to have a more preserved immune system with a higher rate of seroconversion when tested positive for COVID-19 compared to those with hematological malignancies (Sun et al., 2021; A. Thakkar et al., 2021). For instance, Astha Thakkar et al. (2021) studied antibody response rates among 200 cancer patients who received full-dosing of the COVID-19 vaccine and found patients with hematological malignancies had an 85% seroconversion rate compared with 98% among patients with solid tumor malignancies (P=.001).

A study conducted at the University of Arizona evaluated the serological and cellular immune responses after two-dose BNT162b2 vaccination in 53 patients with solid tumors on active cytotoxic chemotherapy compared to control cohort of participants without cancer(Shroff et al., 2021). In patients with solid malignancies, 45.3% and 20.8% were diagnosed with breast and pancreatic cancer, respectively. While overall lower antibody and T cell responses were noted in the solid tumor cohort, 67% of patients with cancer did develop neutralizing antibodies after the first immunization which further increased threefold in median titers after a second dose. The study also reported outcomes of 20 cancer patients enrolled in a phase 1 trial in which a third dose of BNT162b2 was administered. One week following administration of the third dose, 16 patients exhibited a median threefold increase in neutralizing antibody response but no improvement in T cell response. Further evaluation of immune response with potential third vaccine for patients with cancer in under investigation in a phase I trial (NCT04936997).

In a retrospective institutional study measuring the safety and efficacy of COVID-19 vaccination among 122 patients receiving systemic anticancer therapy within 30 days of vaccination, there was no statistically significant difference in all-cause 60-day hospitalization rate between those who received the vaccine within 5 days of anticancer therapy compared to those who received the vaccine between 6 and 30 days from anticancer therapy(Khan et al., 2021). Of note, treatments consisted of chemotherapy (37.7%), immunotherapy (25.4%), combination therapy (27.9%), and targeted therapy (9%). Data suggested safety of the vaccine as close as 5 days from anticancer therapy.

In a German cohort study of 218 patients of which 74.3% had breast cancer and remaining had gynecological cancer, patients had received at least one dose of COVID-19 vaccine while 112 patients had received both doses (Forster et al., 2021). Of the 101 patients with breast cancer, 69 (68.3%) had stage III/IV disease and majority received targeted therapy (32.7%), chemotherapy (28.7%) or endocrine-based targeted therapy (27.7%). In this cohort, 27 patients postponed and 6 declined the vaccine initially. Of the 19 patients with gynecological malignancy in which 18 (94.7%) had stage III/IV disease, 11 patients postponed and 1 declined the vaccine initially. Among the minority of patients that initially postponed or declined the vaccine, there was concern that the vaccine could worsen anti-cancer therapy and lack of evidence regarding vaccine safety among cancer patients. In terms of safety evaluation, the study noted that within 2 weeks of receiving the vaccine, the most frequent side effect included pain at the injection site and fatigue that persisted for the first 48 hours and subsided in 84.9% of patients. No additional side effects were noted with the vaccine administered among patients with breast and gynecological cancers than those noted in the general population.

Among patients with melanoma and renal cell carcinoma receiving immune checkpoint inhibitors (ICI), there remains significant uncertainty regarding the clinical and immunological relationship between contracting COVID-19 and anti-PD-1 therapies (Switzer et al., 2021). Recent data however has suggested that use of ICI does not relate to increased susceptibility or severity of COVID-19 infection when adjusting for confounding factors.(Gambichler et al., 2020; Kuderer & Lyman, 2021; Luo et al., 2020; Pala et al., 2020) There are ongoing trials currently evaluating the COVID-19 antiviral response including immune profiles and clinical outcomes among patients with renal cell carcinoma receiving ICI (NCT03226886). Another trial is also studying the immune response and adverse events after vaccination against COVID-19 among patients with cancer to understand the ability or incapability to mount an immune response after vaccination (NCT04715438).

A unique consideration is the participation in oncology clinical trials with respect to receipt of a COVID-19 vaccine. It is crucial to note that the benefits of the vaccine in mitigating the morbidity and mortality from COVID-19 appreciably outweighs any risk of vaccine-related adverse effect. In patients with solid tumors receiving cytotoxic chemotherapies, COVID-19 vaccine should be administered 1–2 weeks prior to or 1–2 weeks after drug dose if possible, to maximize the potential for immune system to mount a response (Desai et al., 2021). Targeted therapies, hormone therapies, immunotherapy, and epigenetic therapies can be administered on first vaccine availability. For phase I trials consisting of immunotherapy agents with potential risk of cytokine-release syndrome, consider deferral of vaccination until after dose-limiting toxicity window or delay receipt of investigational immunotherapy agent until 2 weeks after vaccine administration. Overall, COVID-19 vaccination should be prioritized in providing quality oncological cares in this high-risk vulnerable population.

Nursing Considerations

The data above highlights the complexity of COVID-19 vaccination planning for patients with cancer and underscores the importance of a multidisciplinary approach (inc. oncologists, infectious disease experts, and nursing). Oncology nurses play an integral role in keeping patients with cancer well-informed about the emerging data on COVID vaccines and how it relates to their disease and treatments with an aim towards providing reliable information from which patients can base their treatment decisions (American Nurses Association, 2022; Carr, 2021). It is important for patients with cancer to understand the impact their disease and treatments may have on their vaccination response and how their vaccination planning will be managed to accommodate for their special needs (i.e., booster dosing, timing vaccinations around cancer treatment to optimize response, antibody titer surveillance). Regarding the vaccination administration, key nursing considerations include the following:

Timing:

COVID-19 vaccines can be administered at any time in relation to other non-COVID-19 vaccines and can be administered simultaneously with other vaccinations. When administered with other vaccines, each injection should be separated by at least one inch. Vaccinations associated with local reactions should ideally be injected in a different limb than the COVID-19 vaccine (Edwards & Orenstein, 2022).

Eligibility:

Patients should be screened for contraindications and precautions to vaccination. Contraindications of COVID-19 vaccination include (1) severe allergic reaction (e.g., anaphylaxis) after a previous dose or component of the COVID-19 vaccine (2) known diagnosed allergy to a component of the COVID-19 vaccine (3) or, for the Janssen COVID 19 Vaccine, thrombosis with thrombocytopenia syndrome (TTS) following receipt of a previous Janssen COVID-19 Vaccine (or other COVID-19 vaccines not currently authorized in the United States that are based on adenovirus vectors) (CDC, 2022).

Administration:

In adults and adolescents, intramuscular vaccines are typically injected into the deltoid muscle, and proper technique is important to prevent shoulder injury. It should be injected at a 90° angle into the central, thickest part of the deltoid muscle (Edwards & Orenstein, 2022).

History of SARS CoV-2 Infection:

COVID-19 vaccination is recommended regardless of history of SARS-CoV-2 infection, and it is not recommended to get pre-vaccination serologic screening to identify prior infection. All recommended doses of a primary series and booster dose should be given, even if SARS-CoV-2 infection is diagnosed after vaccination has been initiated. Patients with a recent infection should be recovered from the acute infection before receiving any of the primary series or booster doses of vaccination (Edwards & Orenstein, 2022). CDC guidance is for infected individuals to meet criteria for discontinuing isolation before receiving vaccination or booster dosing (CDC, 2022).

Conclusion

Patients with cancer are among the most vulnerable to COVID-19 and its most harmful effects. While the immune responses to COVID vaccines in this population may be diminished compared to healthy adults, the vaccines still offer patients with cancer critically needed protection. Oncology nurses play a critical role in helping to guide our patients through the emerging landscape of information on COVID-19 and the vaccines. This information will help patients make informed decisions about vaccination and how to best keep safe from COVID-19.

Key Points.

  • Patients with cancer are highly vulnerable to COVID-19 and its most harmful effects due to immunosuppression.

  • The current FDA-approved/authorized COVID-19 vaccines lacked participation from cancer patients actively receiving treatment in their original studies.

  • While the vaccines offer critical protection for this immunosuppressed group, there are special considerations for nurses to be aware of when administering COVID-19 vaccines to their patients with cancer.

Acknowledgments

This manuscript was funded in part through the NIH/NCI Cancer Center Support Grant P30 CA008748.

Footnotes

Conflicts of interest: None

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