Feature: Vials of Hope: COVID-19 Vaccines for Cancer Patients

Michelle Nguyen, PharmD, BCOP
Clinical Pharmacy Manager, Medical Oncology
New York-Presbyterian Hospital, Columbia University Irving Medical Center
New York, NY

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the resulting illness, coronavirus disease 2019 (COVID-19), have emerged as a global pandemic, with over 20 million confirmed COVID-19 cases in the United States.¹ As the death toll for COVID-19 surpasses the 500,000 mark in the United States, there is a clear need for vaccinating cancer patients to avoid excess morbidity and mortality.1 Large cohort studies have demon­strated that cancer patients are at an increased risk of severe illness from COVID-19.^2-3 Therefore, individuals with active cancer or with active, recent (less than six months), or planned cancer treatment should be considered highest priority to receive one of the COVID-19 vaccines that have been approved by the Food and Drug Administration (FDA) for emergency use authorization (EUA).

How COVID-19 Vaccines Work
Coronaviruses, such as COVID-19, are named for the crown-like spikes on the cell surface, which are called spike proteins and are ideal targets for vaccines. Currently, there are three COVID-19 vaccines that are authorized and recommended in the United States (Table 1). These vaccines work in various ways to offer protection against COVID-19.^4-6

Messenger RNA vaccines, also called mRNA vaccines, offer a new approach to vaccination. Traditional vaccines put a weakened or inactivated germ into the body to trigger an immune response. In mRNA vaccines, cells are given instructions to make a harmless piece of protein called the “spike protein.” These spike proteins are then displayed on the cell surface. This prompts the body to begin building an immune response and making antibodies against COVID-19. There are currently two mRNA vaccines authorized and recommended to prevent COVID-19: Pfizer-BioNTech’s COVID-19 vaccine and Moderna’s COVID-19 vaccine.^4-5

Viral vector vaccines offer another mechanism to help patients develop immunity against COVID-19. A viral vector vaccine contains a modified version of a different virus than the one that causes COVID-19. Inside the shell of the modified virus, there is harmless material from the virus that causes COVID-19. This is called a “viral vector” and stimulates the body to build T-lympho­cytes and B-lymphocytes that will help fight against COVID-19 if infected in the future. There is currently one viral vector vaccine authorized and recommended to prevent against COVID-19: Janssen/Johnson & Johnson (J&J) COVID-19 vaccine.⁶ It is important to emphasize that none of these vaccines can cause infection with COVID-19.

Vaccine Safety and Efficacy
These vaccines have been shown to be safe and effective in the general population. However, the safety and efficacy among cancer patients are unknown. For immunosuppressed patients, the vac­cines do not pose an immediate safety risk as they do not contain a live virus. Systemic side effects with the COVID-19 vaccine tend to occur within two to three days of the vac­cine and may be more pronounced with the second dose. Common side effects include, but are not limited to fever, chills, fatigue, and headache.^4-6 Vaccine safety monitoring systems continue to watch for other poten­tial side effects.

Although each COVID-19 vaccine is unique, all of them may help with herd immunity. Based on the results in clinical trials, the Pfizer-BioNTech vaccine was 95% effective at preventing COVID-19 in people without evidence of previous infection. In addition, the vaccine showed greater than 89% efficacy in prevent­ing people with health conditions, such as diabetes and obesity, from developing symptomatic COVID-19.4 In clinical trials, the Moderna vaccine was 94% effective at preventing COVID-19 in people who received two doses and had no evidence of being previously infected. The vaccine also exhibited greater than 90% effectiveness in preventing people with health conditions from de­veloping symptomatic COVID-19.⁵ Lastly, the Janssen/J&J vaccine was 66% effective at preventing COVID-19 in people who had no evidence of prior infection two weeks after receiving the vaccine. In addition, the vaccine demonstrated to be 100% effective in preventing COVID-19-related hospitalizations and deaths.⁶ People are considered fully vaccinated following two weeks after the second dose for the Pfizer-BioNTech and Moderna COVID-19 vaccine and after the single-dose for the Janssen/J&J COVID-19 vaccine.^4-6

Table 1. COVID-19 Vaccines Approved by the FDA for Emergency Use^4-6

Considerations in Different Types of Malignancies
The National Comprehensive Cancer Network (NCCN) COVID-19 Vaccination Advisory Committee strongly recommends that COVID-19 vaccines be given to all cancer patients.⁷ The rationale of the COVID-19 vaccine in cancer patients is to reduce the risk of COVID-19 morbidity and mortality. Since information on dual vaccination is not available, the COVID-19 vaccine should be priori­tized over other needed vaccines. The recommended timeframe be­tween COVID-19 vaccines and other approved vaccines is 14 days.⁷

Considerations for vaccination timing should also be made for patients receiving cancer treatment (Table 2). Currently, there is no available vaccine data for cancer patients receiving active therapy. However, there is a priority to generate data for this population.

Hematopoietic Stem Cell Transplant (HCT) and Cellular Therapy Recipients
For patients undergoing autologous or allogenic HCT, vaccination may be initiated as early as three months after HCT. In addition, patients who received cellular therapy can be vaccinated as early as three months, if intravenous immunoglobulin (IVIG) independence is demonstrated and B-cell counts ≥ 50 cells/microliter. Patients with controlled graft-versus-host disease (GVHD) should also be considered for the vaccine. There are studies with other vaccines that have shown efficacy in patients with ongoing moderately severe GVHD, without risks of worsening the GVHD. Additional­ly, there is no data to suggest immune activation from COVID-19 vaccines will exacerbate the GVHD. However, it is reasonable to postpone vaccination in patients with severe, uncontrolled acute GVHD grades III-IV.^8-9

Table 2. COVID-19 Vaccination Recommendations for Cancer Patients*⁷

*Adapted from the Preliminary Recommendations of the NCCN COVID-19 Vaccination Advisory Committee

Patients with Hematology Malignancies
Patients with hematologic disease, particularly patients on B-cell depleting therapies, should engage with their oncologist in shared decision making related to optimal timing of vaccination. An intact host immunity is necessary to generate optimal protective immu­nity following vaccination, particularly with respect to B- and T-cell activation and plasma B-cell antibody generation. For patients that have received lymphocyte-depleting therapy (e.g., rituximab, blina­tumomab, anti-thymocyte globulin), consideration can be made to defer vaccination until six months after completion of therapy or until there is evidence of lymphocyte reconstitution (absolute lym­phocyte count [ALC] ≥ 1.0 x103/microliter and/or B-cell counts ≥ 50 cells/microliter). This is because patients with B-cell aplasia will likely not mount a humoral immune response.

For asymptomatic chronic lymphocytic leukemia (CLL), the recommendation is to hold B-cell depleting therapy for one month following completion of the vaccination. For symptomatic CLL, vaccination should be postponed for at least one month following completion of cancer treatment. There should be evidence of B-cell recovery prior to the patient receiving the COVID-19 vaccine. If a patient is on chronic CLL therapy and symptomatic, vaccination should still be considered, as a T-cell memory response may still be generated.

Patients who have acute lymphocytic leukemia (ALL), acute myeloid leukemia (AML), or an aggressive B-cell lymphoma, such as diffuse large B-cell lymphoma (DLBCL), should not delay induction therapy for vaccination. For ALL patients, vaccination can be given during the maintenance phase if there is evidence of hematopoietic count recovery or during induction if a less intense regimen is given. Vaccination for AML patients can be considered during the consolidation phase or if patients have relapsed disease. In B-cell lymphoma patients, vaccination can be administered following completion of therapy and there is evidence of B-cell recovery.^8-9

Patients treated with rituximab clearly have diminished humoral responses to vaccination. One of the highest risk groups for COVID-19 morbidity and mortality are patients treated with rituximab and naturally infected with SARS-CoV-2. It is recom­mended that these patients are vaccinated prior to initiation of therapy when feasible. Since COVID-19 vaccination generates T-cell memory, which may offer partial protection, it is reasonable to offer vaccination even to patients unlikely to mount a B-cell response.^8-9

Solid Tumor Malignancies
Antibody responses to vaccines are generally lower in patients re­ceiving cytotoxic chemotherapy compared with healthy individuals or cancer patients who are not actively receiving treatment. Small studies have yielded conflicting results related to the generation of immune responses, stratified by timing of influenza vaccination in relation to chemotherapy and the nadir period.¹⁰ However, recent reports suggest that timing does not seem to matter.^11-12 Therefore, there is no predefined guidance on the recommended vaccination timing relative to cancer directed medical or radiation therapy. For patients who have planned but not yet initiated cytotoxic treat­ment, the suggested timing of their first dose of the vaccine is two weeks or more prior to start of therapy.⁹

Patients on immune checkpoint inhibitors (ICI) therapy, specifically for lung cancer, are at a higher risk for severe COVID-19. There is conflicting data, but findings suggest that it may be exacerbated by non-therapy related risks and co-existing medical conditions.^2-3,13-14 Patients receiving ICI have also shown to have a more robust humoral and cell-mediated immune response to the influenza vaccine compared to cancer patients receiving cytotoxic chemotherapy.^15-16 However, there is no data to imply that patients receiving ICI experience more immune-related adverse events (irAE) from vaccination. Therefore, the recommendation for patients receiving ICI therapy is that they should receive the COVID-19 vaccine when feasible and ICI therapy does not need to be held for vaccination.⁹

If a patient is receiving high-dose corticosteroids (20 mg per dose or > 2 mg/kg/day of prednisone or equivalent), the immune response may be attenuated in individuals receiving the vaccine. Doses lower than this are unlikely to significantly affect the immune response to a COVID-19 vaccine. Thus, it is recommended that patients treated with high-dose corticosteroids are vaccinated either prior to therapy or after completion of therapy, if possible.^8-9

For patients undergoing cancer-related surgery, there are no spe­cific timing recommendations but there are some considerations. It may be desirable to separate vaccination and a major surgery by a few days or a week. If a patient experiences a side effect, such as a fever, it could be difficult to determine whether it is a vaccine side effect or post-surgical complication.⁹

For many people, the COVID-19 vaccine has offered a beacon of hope in a year of despair. In clinical trials, COVID-19 vaccines have been shown to be effective at preventing COVID-19, especially in severe illness and death. However, information about how effective the vaccines are against variants of COVID-19 are still emerging. The goal is that all patients, with or without cancer, will be safe from contracting COVID-19 through vaccination.

REFERENCES

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