CAPTURE Characterises Cancer Patient Response To COVID-19 Infection, Vaccination

Author: By Lynda Williams, Senior medwireNews Reporter

medwireNews: Patients with haematological malignancy are less likely than other oncology patients to mount a good immune response to SARS-CoV-2 infection or vaccination, suggests research presented at the ESMO Congress 2021.

On behalf of the CAPTURE Study Consortium, Scott Shepherd, from The Royal Marsden NHS Foundation Trust in London, UK, described the functional humoral and cellular immune response to native infection in 118 patients and to two doses of a vaccine in 585 patients.

Specifically, the team used binding antibody response, as well as live virus neutralisation and T-cell activation responses to both the SARS-CoV-2 wild-type virus and the alpha, beta and delta variants of concern (VOC), he explained.

Among the infection cohort, recruited between May 2020 and February 2021, 82% of patients had solid tumours and the majority of patients had mild or moderate COVID-19 symptom severity, the presenter said.

Multivariate analysis showed that neutralising antibodies (NAbs) to wild-type virus were reduced in patients with haematological malignancy, but that age, sex, comorbidity and COVID-19 severity did not significantly impact NAb titres.

Most patients were infected with wild-type or alpha variant virus but analysis indicated that NAb titres were significantly lower against beta and delta variants than the wild-type virus. Longitudinal antibody kinetic analysis revealed that the majority of patients had “durable” binding antibodies for a median of 181 days, with stable titres of NAbs over time, albeit at lower rates against VOC.

SARS-CoV-2-specific T cells were found in the majority of patients, predominantly comprised of CD4+ responses, but haematological malignancy patients were significantly less likely to have a detectable T-cell response than their solid tumour counterparts, said Scott Shepherd.

But the investigator noted that among the haematological malignancy patients there was a “disconnect between the arms of the immune response”. In particular, the lymphoma patients – the majority of whom had received anti-CD20 monoclonal antibody treatment in the past year – had undetectable humoral responses after COVID-19 infection but higher T-cell activation “suggestive of immune compensation for the lack of antibody response”, he remarked.

Further multivariate analysis showed that different anticancer treatments and comorbidity did not impact cellular response to COVID-19, except for suppression of CD4+ T-cell activation in patients given immune checkpoint inhibitor therapy.

“It is reassuring, however, that large-scale registry data sets have not indicated that this group are at an increased risk of severe COVID-19 and we believe therefore [that] this finding is of limited clinical significance”, he emphasized.

Turning to the vaccination cohort, Scott Shepherd said that the majority (76%) of the group had solid tumours, had received the AstraZeneca vaccine (74%) and did not have prior COVID-19 infection (69%).

At 14–16 weeks after the second vaccine dose, 78% of patients had binding antibodies against the wild-type virus spike protein, and live virus NAb assessment indicated there were detectable NAbs against the wild-type virus in 83%. However, significantly fewer patients had NAbs against the alpha, beta and delta VOCs, at 61%, 53% and 54%, respectively.

This demonstrates “that measuring binding antibodies to wild-type spike, as is routine in clinical practice, may overestimate protection to variants of concern and might be falsely reassuring to patients regarding their degree of protection from infection following vaccination”, cautioned the presenter.

And he highlighted a significant reduction in NAbs, especially among VOC, in haematological malignancy patients compared with solid tumour patients.

Multivariate analysis indicated that chemotherapy, targeted therapy, immunotherapy and immunosuppressive treatments, such as steroids, did not significantly impact NAb response in vaccinated cancer patients, with the exception of receipt of anti-CD20 therapy in the prior 12 months.

Furthermore, Scott Shepherd reported that cancer patients with prior COVID-19 infection had a significantly stronger NAb response than those without, including NAbs against the delta VOC (80 vs 53%).

“These data would appear to lend support to a third primary vaccination in patients with cancer to boost their humoral response”, he commented.

The presenter also showed data for cancer patient NAb activity compared with that found in healthy individuals participating in the LEGACY study. When assessing NAb response by age, patients with haematological malignancy had a significantly lower NAb response than LEGACY participants, whereas a comparable NAb response was found among the solid tumour patients and controls of similar age.

Finally, T-cell response analysis showed peripheral blood cell activation against wild-type virus in 79% of cancer patients after two doses of vaccine, as well as activation against both the alpha and delta VOC.

A similar proportion of patients with haematological malignancies and solid tumours had detectable T cells after vaccination, the investigator said, and age, sex or comorbidity did not predict T-cell response, and responses were found in patients without a humoral response, such as those given anti-CD20 therapy.

Scott Shepherd concluded: “Ongoing efforts to define precise correlates of protection are needed to individualise patient management and inform risk mitigation strategies for patients with cancer and their carers.”

Reference

1157O - Shepherd STC, Fendler A, Au L, et al. Adaptive immunity to SARS-CoV-2 infection and vaccination in cancer patients: The CAPTURE study. Ann Oncol 2021;32(suppl_5):S1129–S1163. doi:10.1016/annonc/annonc713