COVID-19 vaccines have been proven to be effective in immunocompromised patients, in particular patients with cancer; however the level of protection they offer is lower than that in the general population and there is evidence of greater waning of immunity with time progression (1). Thus, there is a higher risk of COVID-19 associated hospitalisation and serious complications in patients with cancer, and we have subsequently observed higher mortality in this vulnerable population since the start of the pandemic.
What did our research show?
Our study explored the relationship between cancer type, treatment type, vaccine type received and the effect this can have on COVID-19 vaccine efficacy in patients with cancer (1). We found patients with haematological cancers on active anti-cancer therapies had significantly lower immunogenicity in comparison to patients with solid cancers and the immunocompetent population, making them more susceptible to infection with Sars-COV-2 virus. Additionally, our findings show a significant difference in vaccine efficacy depending on the type of vaccine received by patients with cancer - three studies included in our analysis concluded that the MDN vaccine regimen induces a higher serological response in patients with cancer in comparison to those who received the BTN vaccine. This suggests a preference for the MDN vaccine in this immunocompromised population based on immunogenicity, safety and efficacy of the MDN vaccine and is the most readily modifiable factor to aid patients with cancer to maximise their chance of mounting a strong immune response post vaccination.
The type of treatment received was found to significantly affect vaccine efficacy and waning of antibodies. Bruton Tyrosine Kinase inhibitor therapy was found to be a robust predictor of seronegativity, of which many patients with haematological cancers were receiving. Further to this, B cell depleting therapies such as anti-CD20 monoclonal antibodies also resulted in significantly lower rates of seroconversion in recipients. Of interest, patients who were not currently receiving anti-CD20 antibodies or BTKi therapy but had previously received these therapies also failed to mount a significantly high immune response. Two studies also evidenced poor seroconversion in patients actively receiving chemotherapy treatment, however this was to a lesser extent than that seen with BTKi therapy and anti-CD20 therapy. Immunotherapy induced better immunity after vaccination in cancer patients, but overall treatment naive patients fared the best with higher rates of seropositivity than patients on any form of systemic anti-cancer therapies. This remains a challenge as many patients with cancer are on some form of therapy which is vital to prevent disease progression and reduce the risk of mortality.
What next?
Although our findings highlight the importance of booster vaccinations in cancer patients and the maintenance of infection prevention measures to reduce risk of infection, the failure to mount any immune response at all demonstrated by some patients underlines the need for more novel treatments to induce antibody protection, prevent disease progression and ultimately reduce the burden on healthcare systems (2). Pre-exposure prophylactic antibodies have recently been under discussion as a potential tool in ensuring patients with cancer are receiving the full support and protection they need as normality resumes in the presence of SARS-CoV-2 virus. Evusheld is the particular drug of interest and is a combination of two long-acting neutralising antibodies - Tixagevimab and Cilgavimab. These antibodies are obtained from the B cells which are donated by individuals previously infected with Sars-CoV-2 virus, and bind to specific domains on the SARS-CoV-2 spike proteins, acting to prevent the risk of contracting SARS-CoV-2 virus. A single intramuscular dose of this drug has been shown to significantly reduce the risk of contracting this virus, but also reduce the risk of severe disease in symptomatic patients (3).
Evusheld has been found to be effective up to six months after administration and has also been shown to reduce the risk of respiratory failure and therefore possible mechanical ventilation. In an ongoing phase III treatment trial, PROVENT, a single intramuscular dose of Evusheld in the AZD7442 group resulted in a relative risk reduction of 82.8% at a median of six months in comparison to the placebo group (3). A similar efficacy was observed in more vulnerable subgroups such as participants with increased risk of exposure to Sars-COV-2 virus or decreased chance of seropositivity, with relative risk reductions of 80.7% and 82.6% respectively. Additionally, there was a longer time until symptomatic illness with COVID-19 in the AZD7442 group than the placebo group that did not receive Evusheld, and no safety concerns of interest were raised during this trial. Data from PROVENT indicates that Evusheld is an effective form of immunoprophylaxis in immunocompromised patients and is an effective solution to the diminished immune response observed in cancer patients after all doses of the COVID-19 vaccinations (3).
Take home message
While vaccination and booster doses remain the default for the healthy population, prophylactic antibody treatment is a revolutionary turning point for patients with cancer who generally demonstrate seronegativity after all doses of the COVID-19 vaccination. Many immunocompromised patients are continuing to shield and this has severely impacted on their quality of life and is not a sustainable solution to “live with coronavirus”. The decision to abandon the purchase of this drug by the government despite its proven clinical effectiveness leaves this vulnerable patient population with very little protection and it is hard to defend the accusation by patient groups that they have been abandoned by policy makers (4).
Approval and delivery of this treatment is desperately needed to improve morbidity and mortality rates in patients with cancer, particularly as we approach the winter period where infection rates are likely to increase, putting patients with cancer at even greater risk of hospitalisation, intensive care admission, death and significantly disrupted cancer care.
References
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