Samra Turajlic's lab working on the CAPTURE project.
A third dose of the COVID-19 vaccine could increase protection from COVID-19 for people with cancer, and especially blood cancer, according to a new study from the Francis Crick Institute and The Royal Marsden NHS Foundation Trust published today in Nature Cancer (27 October).
In the CAPTURE study, funded by The Royal Marsden Cancer Charity, researchers monitored the immune response of 585 patients with different types of cancer after receiving a first and second dose of the COVID-19 vaccine (Pfizer-BioNTech or Oxford-AstraZeneca).*
This is the largest study to comprehensively evaluate the response of patients with cancer to COVID-19 vaccines.
Using a highly accurate test, a viral neutralisation assay developed at the Crick, the researchers measured levels of antibodies which block different strains of the virus, including the Delta variant, into cells. These so-called ‘neutralising antibodies’ are different to antibodies that are measured routinely. The researchers used this more informative test to see if the patients had levels of neutralising antibodies which were sufficient to block at least 50% of virus infection under laboratory conditions.**
After two doses of the vaccine, 83% of patients previously not infected with the virus developed neutralising antibodies against the original strain, which is no longer in circulation but is the strain current vaccines were designed to target.
However, when the researchers looked at antibodies able to neutralise the Delta variant, only 54% of patients developed these after both vaccine doses (31% of patients with blood cancer and 62% of patients with solid cancers; 68% of patients vaccinated with the Pfizer-BioNTech and 50% of patients vaccinated with the Oxford-AstraZeneca vaccine).
Patients with blood cancer were less likely to have antibodies than individuals of a similar age without cancer or with solid cancer, and when they did have antibodies, the levels were lower against all variants. Patients with solid cancer had an antibody response that was more comparable to individuals without cancer.
Importantly, neutralising antibody responses against the Delta variant were higher in vaccinated patients with cancer who had previously been infected with SARS-CoV-2, compared with those who had no previous infection (57% compared with 31% for patients with blood cancers; and 86% compared with 62% for patients with solid cancers). This suggests that a third dose could effectively boost immunity for vulnerable patients.
When comparing their results with those from commonly used antibody tests for SARS-CoV-2, they found that tests that don’t look specifically at circulating variants of concern can overestimate the level of neutralising antibody protection in an individual, especially in relation to the Beta and Delta variants.
The researchers also found that age and vaccine type were linked to immune responses to vaccines. Older patients developed lower levels of neutralising antibodies,*** and patients with solid cancer vaccinated with Oxford-AstraZeneca had lower responses than those vaccinated with Pfizer-BioNTech, as has been shown in individuals without cancer. Most cancer treatments, especially for solid cancers, did not impact the immune response to the vaccine, with the exception of anti-CD20 therapy which was linked to an absence of neutralising antibodies.
Previous research from others has suggested that if a patient has higher levels of neutralising antibodies, they have a lower risk of breakthrough infection. However, the exact immune response for individuals varies and for some patients, lower levels of neutralising antibodies may still be associated with some protection against infection and protection from severe COVID-19.
To comprehensively understand how vaccinations protect patients with cancer against COVID-19, the researchers also assessed T cell responses to vaccines. They found that 79% of vaccinated cancer patients developed a T cell response and the T cell response was the same in patients with solid and blood cancers. Importantly, the vaccines induced T cells in patients who did not have a neutralising antibody response. This was in keeping with their observations that some patients with blood cancer who recovered from COVID-19 did not have neutralising antibodies but did have a strong T cell response. Further work will be needed to fully understand how T cells contribute to protection.
Dr Samra Turajlic, lead author and group leader at the Crick and Consultant Medical Oncologist at The Royal Marsden NHS Foundation Trust, said: “While patients with blood cancer are more vulnerable to severe symptoms of COVID-19, there is a limited understanding of how they respond to vaccines, especially in the context of the circulating Delta variant. This makes it harder for patients to make informed decisions about their level of risk - especially as social contact restrictions have been lifted - and for their doctors to decide on the right risk reduction strategy.
“This study provides evidence that variants of concern pose a greater threat to some patients with cancer, specifically those with blood cancer. Our findings support the argument that these people should be prioritised to receive a third vaccine dose. For patients with solid cancer, appropriateness of a third dose may depend on their age, vaccine type, and previous infection. Prioritisation of a third dose should also take into account how the COVID-19 infection may disrupt an individual’s anti-cancer treatment.
“We urge that patients with cancer, but especially those with blood cancer and on certain cancer therapies, continue to take precautions to protect themselves - especially in situations where there is a higher risk of transmission, such as in crowded spaces and indoors. The data highlight that future emerging variants may pose additional risks to patients with cancer. Reinstating simple public health measures, such as wearing masks in public transport and other indoor spaces, will help to protect and reassure vulnerable patients with cancer, their carers and healthcare workers. Such measures can also reduce the indirect impact of the pandemic on cancer patients caused by disruption of healthcare services.”
In September, the Joint Committee on Vaccination and Immunisation (JCVI) issued advice recommending that immunosuppressed adults should receive a third primary dose this autumn. This includes patients with blood cancer and patients with solid cancer receiving immunosuppressive chemo- or radiotherapy. Researchers from the CAPTURE study have submitted their findings to the JCVI, as evidence of the level of protection cancer patients have against the variants of concern.
This study is led by the Royal Marsden NHS Foundation Trust, funded by The Royal Marsden Cancer Charity, and received support from the NIHR Biomedical Research Centre at The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research, London.
Notes
*93% of patients (546) received both a first and second dose of vaccine.
** Neutralising antibodies (NAb) are measured in serial dilution of serum. Neutralising antibody titres represent the fold-dilution of the serum in which 50% of the virus is inhibited. Neutralising titres are undetectable/low if no inhibition is seen or if less than 50% of inhibition of the virus is observed in the lowest dilution.
*** As patients in this study were relatively young (60 years on average), the researchers warn that older patients with cancer may have even lower levels of antibodies against the Delta variant than those observed in this study.
