Data support third COVID-19 vaccine dose for some patients with cancer
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COVID-19 variants pose a greater threat to certain patients with cancer, particularly those with hematologic malignancies, confirming the need to promote vaccination within this population, according to data presented at ESMO Congress 2021.
“Patients with cancer who have been exposed to the virus through infection and had two vaccine doses had higher levels of immune response against the delta variant. Our findings support the argument that some [patients with cancer], especially patients with blood cancer, should be prioritized to receive a third primary vaccine dose,” Scott Shepherd, MD, clinical fellow in the cancer dynamics laboratory at The Francis Crick Institute in London, told Healio.
Shepherd presented results of CAPTURE, a prospective longitudinal cohort study of COVID-19 vaccine or SARS-CoV-2 infection-induced immunity, during the virtual conference.
Age, vaccine type and previous infection should all be considered in determining the appropriateness of a third dose among patients with solid cancer, and prioritization also should consider how SARS-CoV-2 infection may disrupt an individual’s anticancer treatment, Shepherd added.
Shepherd and colleagues undertook the research because patients with cancer are at increased risk for severe COVID-19 outcomes, and understanding the impact of infection and vaccination induced-immunity remained an unmet need.
“Our aim was to study functional immune responses to both infection and vaccination, integrating clinical annotation to explore the impact of disease- and treatment-specific factors on immune responses in patients with cancer,” Shepherd said.
The analysis included 118 patients with confirmed SARS-CoV-2 infection and 585 vaccinated patients with cancer. Shepherd and colleagues followed the patients longitudinally, assessing binding antibody responses; live virus antibody responses to both wild-type SARS-CoV-2 and alpha, beta and delta variants of concern; and for the presence of SARS-CoV-2-specific T cells.
Results within the infection cohort showed:
- infection led to durable neutralizing responses in most patients with cancer, but patients with hematologic malignancies had reduced responses;
- the majority of patients with cancer had detectable cellular response to infection, but significantly fewer patients with hematologic malignancies had detectable T-cell responses;
- neutralizing responses to beta and delta variants were reduced compared with wild-type SARS-CoV-2; and
- anticancer treatments generally did not impact immune response, with the exception of anti-CD20 monoclonal antibodies and immune checkpoint inhibitors.
Most patients (76%) in the vaccine cohort had solid cancers and 74% received the vaccine developed by AstraZeneca and University of Oxford. Results in this cohort indicated patients with hematologic malignancies had reduced or absent neutralizing activity against variants of concern, whereas patients with solid cancers had activity comparable to noncancer controls, and that previous SARS-CoV-2 infection boosted vaccine-induced responses, thus supporting a third booster dose. Also within the vaccine cohort, researchers found that assessing anti-S1 antibodies may overestimate protection against variants, anticancer therapies (other than anti-CD20) did not affect neutralizing responses, and most patients had SARS-CoV-2 specific T-cell responses.
Shepherd stressed the need for ongoing efforts to define precise correlates of protection from breakthrough infection.
“We were encouraged that the majority of patients develop immune responses to both vaccination and previous SARS-CoV-2 infection; however, it is of concern that responses to variants of concern are diminished,” Shepherd said. “We would strongly encourage patients to have a third vaccine dose to boost immunity to the delta variant.”
Perspective
Back to TopMarie von Lilienfeld-Toal, MD
Patients with hematologic malignancies have a diminished serologic response compared with patients with solid tumors. This possibly is not the same and does not apply to all kinds of hematologic malignancies, although that finding is not completely robust yet. It does seem, though, that anti-CD20 therapy really diminishes the antibody response to almost zero in almost all patients. In contrast, T-cell response seems to be more robust and comparable in patients with hematologic malignancies and those with solid tumors.
However, variants of concern are of particular concern in patients with hematologic malignancies since they cannot be as well-neutralized as the wild type, as we see in the CAPTURE study, whereas we see patients with solid tumors still have a neutralizing capacity against the delta variant, which is almost zero in patients with hematologic malignancies, leaving them without a meaningful protection against variants of concern.
We have also learned that the immunologic profile after vaccination resembles that after infection, so the neutralizing capacity is possibly better after infection; but it is there in patients with cancer.
Similar to the patients after vaccination, the serologic response does not always correlate with a T-cell response. But sometimes T cells can be detected where the serological response is missing, possibly suggesting some compensatory mechanism.
Overall, most importantly, we’d like to learn more about the clinical efficacy and to understand how this correlates with immunologic outcomes parameters. We have reason to believe the clinical efficacy is going to be high.
How can the protection of [patients with cancer] be improved? The first and most important thing to do is to vaccinate everybody around. Just do it. Just vaccinate patients and vaccinate the community.
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Shepherd STC, et al. Abstract 15570. Presented at: European Society for Medical Oncology Congress (virtual meeting); Sept. 17-21, 2021.
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