COVID-19 vaccination of patients with cancer: Do's and Don'ts.

Dear Editor,

It has been over 1 year since COVID-19 came into existence. With extraordinary efforts of our scientists, we have vaccines against this deadly virus within a year itself. Now, as the health care system across the globe is bracing up to vaccinate their citizens, the real question for oncologists is whether it is safe to vaccinate patients with cancer. In this letter, we will try to answer few common concerns and questions regarding vaccinating patients with cancer and the involved risks and benefits.

Pfizer-BioNTech and Moderna COVID-19 vaccines are among the most studied and so far being readily used in the United States. Both are messenger RNA COVID-19 vaccines, lipid nanoparticle formulated, and nucleoside modified. The manufacturers have laid down the indications, contraindications, and expected side effects related to these vaccines. Similarly, in India, two available vaccines are Covishield (AstraZeneca's vaccine manufactured by Serum Institute of India) and Covaxin (manufactured by Bharat Biotech Limited). Covaxin, a home-grown vaccine by combined collaboration of Hyderabad-based Bharat Biotech International Ltd. and the Indian Council of Medical Research, has shown an efficacy rate of 81% compared with Pfizer-BioNTech, which is reported to be 95.3% effective against severe COVID-19.

During the development of the vaccine, cancer patients on active treatment (chemotherapy or immunotherapy) were excluded from the study. Similarly, vaccine efficacy and side effect profile were not studied in pregnant women, children, and immunocompromised individuals. Hence, no clear-cut recommendations are available for patients with cancer. This has put the cancer society in a state of dilemma if whether to advice vaccination to their patients or not once it is available.

The Centers for Disease Control and Prevention's (CDC) Advisory Committee on Immunization Practices has formulated a three-phase program (Fig. 1). Based on their recommendations, patients with cancer would fall into the phase 1b/c category. To streamline the vaccination policy and help the community oncologists in decision-making process, various hematology and oncology society and experts have begun holding webinars and conferences to suggest interim guidelines., Dr. Gary Lyman from Hutchinson Institute, Fred Hutch, suggested that lessons can be learned from the flu shot we give yearly to our cancer patients in between cycles. It is believed that the risk of complications and mortality once COVID-19 is acquired will be far more than the risk of any side effects related to getting vaccinated., The national comprehensive cancer network has recently published the preliminary recommendations based on panel discussion involving experts from various specialties. It suggests vaccination for all patients with cancer even while receiving active therapy. Priority to vaccinate should be given to the patients who are planned to undergo radical surgery and are subsequently candidates for adjuvant systemic treatments. Patients who have recently undergone surgery are recommended to wait for at least 2 weeks before receiving a vaccine. The Cancer Clinical Trials Working Group from the United States has recently suggested COVID-19 vaccine guidance for patients with cancer participating in oncology clinical trials. Their proposal for the cancer patients who are enrolled in surgery clinical trials is to give COVID-19 vaccine after recovery from postoperative complications at discharge or 1 week before surgery. However, oncologists should inform their patients that as of now, there are limited safety and efficacy data. The discussion becomes more pertinent in lieu of recent reports of clot-related deaths following Oxford-AstraZeneca vaccination in recipients. Inherently, patients with cancer have higher chance of thrombosis; however, currently, World Health Organization states that the advantages of the AstraZeneca vaccine outweigh its risks and recommends that vaccinations to be continued., Unfortunately, there are no comparative data on the various types of vaccines used and their impact on cancer patients to prove or negate increased chance of clot development particularly with the Oxford-AstraZeneca vaccine in cancer patients. Till we have more firm data, we believe that it would be a shared decision-making, which will lead the way.

Fig. 1

Various phases of vaccination drive suggested by CDC's Advisory Committee on Immunization Practices.

Patients who underwent Hematopoietic stem cell transplantation (HSCT) or cellular therapy (e.g. CAR-T cells) are recommended to wait for 3 months before receiving the first dose of the vaccine (Fig. 2).

Fig. 2

NCCN recommendations regarding vaccination of patients with cancer (version 1.0 1/22/2021).

With regard to the patients who already have suffered from COVID-19 disease, the CDC has mentioned guidelines for vaccination as well. As per them, vaccination should be postponed till recovery from the COVID-19 acute illness and have met all the criteria to discontinue isolation. Patients who received monoclonal antibody or plasma therapy should be deferred from getting vaccination for at least 90 days. The CDC guidelines do not mention specifically for vaccination of cancer patients post-COVID-19 infection. However, Memorial Sloan Kettering Cancer Center (Version 4, Date: 03.10.2021) guidelines suggest to follow the same guidelines similar to the patients without cancer.

The demand and supply discrepancy are expected to come our way while vaccinating for COVID-19. There may be scenarios where oncologists need to prioritize one patient with cancer over the other due to the limited availability of vaccine. The National Comprehensive Cancer Network has also acknowledged this shortcoming in our production and distribution system and has recommended to follow the local-/state-specific vaccine guidance on allocation. The NCCN suggested the following patients with cancer should be considered on priority when such circumstances prevail:

Patient with active cancer on treatment

Patient with active cancer and are planned to be started on treatment

Patient with immediately (<6 months) posttreatment period

Patient with active cancer and co-existent additional risk factors, which make patient prone to adverse COVID-19 complications.

NCCN panel, however, could not recommend prioritization for vaccine allocation based on the type of cancer (hematologic versus solid tumors) and type of treatment (chemotherapy, surgery, radiotherapy, or immunotherapy). NCCN panel suggested that the only definite low priority group are the patients without active cancer who are receiving hormonal therapy only.

One of the most daunting tasks that researchers have faced during COVID-19 pandemic is to smoothly run the cancer-related trials. One of the recent studies by Lamont et al showed that of the 1440 Phase 1–4 oncology trials that were launched in 91 countries during the 40-month observation period, 1249 were started in the years before the COVID-19 pandemic, but just 191 since COVID-19 hit the globe. From vaccination perspective, Desai et al from Cancer Clinical Trials Working Group have advocated for patient prioritization and recommended for vaccination of the patients who are actively participating in the trials.

At present, vaccine studies are underway on patients with cancer who are in naïve stage (Phase 1C), but probably most of the data on the vaccine safety are expected to come from the field where oncologists and patients with cancer would agree to proceed with vaccination based on shared decision-making. Currently, the recommendations can only come from the observational data because results from randomized controlled trials to the said effect do not exist. An obvious downside of following these recommendations would be to suffer from all the pitfalls of relying on observational data where correlations may be get confused with causation. We believe that there is still gap in knowledge and understanding in this aspect and newer updates are expected in the coming months.

Ethical statement

The article does not contain the participation of any human being and animal.