Patients with cancer are at high risk for complications and death from COVID-19 infections, but vaccination offers patients with solid tumors strong protection against SARS-CoV-2, including the Delta variant. Patients with hematologic malignancies, however, are less likely to mount a strong immune response to vaccination, possibly due to the natural history of the disease and to B cell–depleting therapies that affect antibody responses.
Patients with solid tumors who are receiving chemotherapy and/or immunotherapy get the same level of protection from vaccination against COVID-19 as people without cancer, but natural immunity from SARS-CoV-2 infection in patients with cancer can vary widely depending on the viral variant in question.
In addition, patients with hematologic malignancies don't seem to get as strong a benefit from vaccination as patients with solid tumors.
Those conclusions come from two separate studies presented at the European Society for Medical Oncology (ESMO) Congress 2021: The VOICE study assessed how therapy might affect vaccine efficacy in patients with solid tumors; CAPTURE looked at immune responses in two cohorts of patients with cancer, one group after vaccination and the other after SARS-CoV-2 infection.
In the VOICE trial, antibody response rates 4 weeks after the second dose of the mRNA-1273 vaccine (Spikevax; Moderna) were 100% or slightly below—and were virtually indistinguishable between healthy controls and patients with solid tumors who were receiving chemotherapy, immunotherapy, or both, reported Sjoukje Oosting, MD, PhD, of the University Medical Center Groningen in the Netherlands.
Adequate antibody responses, defined as a minimum of 300 binding antibody units (BAU)/ml, were seen after the first dose in 66% of controls, 32.5% of patients undergoing chemotherapy, 37.1% of patients taking immunotherapy, and 33.3% of those receiving chemo-immunotherapy. Twenty-eight days after the second dose, adequate antibody responses increased to 99.6%, 83.8%, 93.1%, and 88.8%, respectively.
Among patients who had inadequate or undetectable antibody responses to mRNA-1273, T-cell responses to the spike protein of SARS-CoV-2 were detectable in 46.7%.
Safety of the vaccine in patients with cancer was similar to that seen in healthy controls, and no new safety concerns were uncovered, researchers said.
“Possibly the most important result from the VOICE trial is the very clear finding that patients with solid tumors mount a robust serologic response, very much comparable to that of healthy controls, and this is independent of the therapy they receive,” commented ESMO discussant Marie von Lilienfeld-Toal, MD, PhD, of University Hospital Jena in Germany.
In the prospective, longitudinal CAPTURE study, conducted in multiple centers in the UK, investigators reported that rates of detectable serum antibodies (seroconversion) in patients with cancer after two doses of either the BNT162b2 mRNA vaccine (Comirnaty; Pfizer/BioNTech) or the conventionally designed AZD1222 vaccine (Vaxzevria; Covishield; AstraZeneca) were 85% among patients with solid tumors vs. 59% in those with hematologic malignancies.
Compared with healthy controls, patients with hematologic cancers had reduced neutralizing antibody responses, but patients with solid tumors had responses similar to people without cancer.
The CAPTURE team also found that in a separate cohort of 118 patients with cancer who were SARS-CoV2–positive, 83% had reactive antibodies to the S1 subunit of SARS-CoV-2 and 82% had neutralizing antibodies against the wild-type virus, but “substantially lower” neutralizing antibody responses to viral variants of concern, such as the notorious Delta variant, which currently accounts for the vast majority of COVID-19 infections in the United States and Europe, said Scott Shepherd, MD, of the Francis Crick Institute in London, UK.
“Whereas patients with solid tumors still have a neutralizing capacity against the Delta variant, this is almost zero in patients with hematological malignancies, leaving them without a meaningful protection against variants of concern,” von Lilienfeld-Toal said.
Although antibody responses were notably diminished in patients with hematologic cancers, vaccine-induced T-cell responses were detectable in 80% of patients in this trial and were comparable between both vaccine types and between patients with either solid or hematologic malignancies, suggesting a compensatory mechanism, she added.
At least some differences between solid and hematologic cancers may be explained by B cell–depleting therapies, such as CD20 inhibitors, JAK inhibitors, or other therapies that dramatically reduce antibody responses, she said. –Neil Osterweil