Patients with cancer have been prioritized in vaccination programs due to the increased likelihood of poor clinical outcomes from a SARS-CoV-2 infection. However, there has been limited data on the impact of cancer and anticancer therapies on immune responses to the virus in this population.
At the virtual European Society for Medical Oncology Congress 2021, researchers presented results from the CAPTURE trial, a prospective, longitudinal cohort study aimed at characterizing functional immune responses to native infection and vaccination in patients with cancer.
Among patients with cancer vaccinated against SARS-CoV-2, those with hematologic malignancies had reduced or absent neutralizing activity against variants of concern (ie, delta), whereas patients with solid cancers had levels comparable to those of noncancer controls, said Scott Shepherd, MD, Clinical Research Fellow, The Royal Marsden Hospital, NHS Foundation Trust, London, Great Britain, who presented the results of the study.
“While the majority of patients with cancer have detectable binding antibodies following infection or vaccination, these are reduced in patients with hematological malignancies, and in particular, those receiving anti-CD20 monoclonal antibodies,” he said.
A total of 118 patients with confirmed SARS-CoV-2 infection and 585 who received a COVID-19 vaccine were recruited for the study. Patients were followed longitudinally for binding antibody response, live virus neutralization to both wild-type SARS-CoV-2 and variants of concern, and the presence of SARS-CoV-2–specific T-cells.
In the 118 patients with cancer (97 with solid tumors, 21 with hematologic malignancies) with confirmed SARS-CoV-2 infection, asymptomatic infections were identified in 24.
“The majority of the cohort had either mild or moderately severe COVID-19 according to the [World Health Organization] severity criteria,” Dr Shepherd said.
SARS-CoV-2 infection was found to induce robust and durable neutralizing responses in most patients with cancer.
“In a multivariate model, we found that these were reduced in patients with hematologic malignancies,” he said. “We did not observe any impact of comorbidity, age, gender, or COVID-19 disease severity on neutralizing antibody titers.”
Approximately 84% of the patients with infection were infected with wild-type SARS-CoV-2. Neutralizing titers were reduced significantly to the delta and beta variants compared with wild-type.
Most patients had durable binding antibodies for a median of 181 days and up to 11 months. Neutralizing antibody titers remained stable over time, although responses were lower in the context of variants of concern.
The majority of patients had a detectable SARS-CoV-2–specific T-cell response following infection, although CD4-positive responses predominated over CD8-positive T-cell responses. T-cell responses, in particular the CD4-positive responses, were reduced in patients with hematologic malignancies.
A disconnect between the arms of the immune response was observed in those with hematologic malignancies.
“Patients with lymphoma, most of whom received anti-CD20 monoclonal antibodies within the previous 12 months, all had undetectable humoral responses following infection, but they compensate for this through higher T-cell activation, suggestive of immune compensation for the lack of antibody response,” Dr Shepherd said.
“This finding potentially reconciles recovery from severe COVID-19 in patients without detectable antibodies.”
There was no effect of anticancer therapies or comorbidities on cellular responses. The one exception was lower T-cell activation in patients treated with immune checkpoint inhibitors, Dr Shepherd noted. This group does not appear to be at increased risk for severe COVID-19 based on large registry data, he added.
Responses to vaccination were assessed in the 585 vaccinated patients, who were found to have seroconversion rates of 85% (solid tumors) and 54% (hematologic malignancies) after 2 doses of vaccines administered 12 weeks apart. However, neutralizing antibodies to variants of concern were reduced significantly compared with the wild-type, with only 54% of patients with cancer having neutralizing antibodies to the delta variant versus 84% to the wild-type.
“This demonstrates that measuring binding antibodies to wild-type spike, as is routine in clinical practice, may overestimate protection to variants of concerns, and might be falsely reassuring to patients regarding their degree of protection from infection following vaccination,” he said.
Patients with hematologic malignancies were more likely to have undetectable neutralizing antibodies, regardless of subtype, and had lower neutralizing antibody titers compared with those with solid malignancies to both wild-type and variants of concern.
Anti-CD20 treatment within the previous 12 months had profoundly suppressed neutralizing activity.
Previous SARS-CoV-2 infection in vaccinated patients boosted the number of neutralizing antibodies, which lends support to a third vaccine dose in patients with cancer, Dr Shepherd said.