COVID-19 vaccination safe, effective during treatment for solid tumors
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The mRNA-1273 COVID-19 vaccine appeared safe and effective during treatment with immunotherapy and chemotherapy among patients with solid tumor cancers, according to results of the VOICE trial presented during the virtual ESMO Congress 2021.
“Patients with cancer have a higher risk for complications, including ICU admissions and mortality, from COVID-19 and professional societies recommended early on to prioritize patients with cancer for vaccination. However, there were no data on safety and efficacy of COVID-19 vaccination during treatment with chemotherapy or immunotherapy for solid tumors, as these patients were not included in the registration trials,” Sjoukje Oosting, MD, PhD, oncologist at University Medical Center Groningen in the Netherlands, told Healio. “There was a need to assess the impact of chemotherapy and immunotherapy on the ability to mount an effective immune response to vaccination, as well as to assess safety by investigating local and systemic side effects and adverse events.”
The prospective, multicenter, noninferiority trial included 743 adults, including 240 individuals without cancer and patients with solid tumors treated with immunotherapy alone (n = 131), chemotherapy alone (n = 229) or chemotherapy plus immunotherapy (n = 143). All participants received both doses of the mRNA-1273 (Moderna) COVID-19 vaccine.
COVID-19 antibody response, defined as less than 10 binding antibody units/mL 28 days after the second dose, served as the primary endpoint. Investigators also assessed viral neutralizing capacity of antibodies, COVID-19 spike-specific interferon-gamma T-cell response and adverse events.
Results showed an antibody response at day 28 after the second dose among 100% of individuals in the control group, 99.2% of patients in the immunotherapy group, 97.4% in the chemotherapy group and 100% in The chemoimmunotherapy group.
“The antibody response was much higher than we expected,” Oosting said. “When we wrote our protocol, we assumed that 90% of controls and 90% of patients receiving immunotherapy would have seroconversion and that this would be significantly lower among those receiving chemotherapy — we estimated 60% based on influenza vaccination studies.”
Researchers then defined a cutoff level at 300 BAU/mL based on neutralizing capacity to differentiate between suboptimal and adequate responders. They observed an adequate antibody response after the first vaccine dose among 66% of controls, 37.1% of the immunotherapy group, 32.5% of the chemotherapy group and 33.3% of the chemoimmunotherapy group, which increased 28 days after the second dose to 99.6%, 93.1%, 83.8% and 88.8%, respectively.
In addition, spike-specific T-cell responses were detected in 46.7% of suboptimal and non-responders. Of note, researchers observed no new adverse events.
“The seroconversion rate in patients was not inferior compared with controls. We also defined a threshold for an adequate antibody response and found that the majority of the patients develop an adequate response after two vaccinations. However, a substantial minority doesn’t — 6.9% of those receiving immunotherapy, 16.2% of those receiving chemotherapy and 11.2% of those receiving chemoimmunotherapy,” Oosting said. “We found that in most patients, the antibody concentration increased after the second vaccination, which supports the idea that a third vaccination can turn suboptimal responders into adequate responders.”
Oosting and colleagues are now examining the effect of a third vaccination dose among individuals with suboptimal antibody response.
“It will also be crucial to see if there is a difference in duration of response between patients and controls; we therefore have follow-up assessments at 6 months and 12 months after the last vaccination,” Oosting said. “The CAPTURE study, presented by Scott Shepherd, MD, during the presidential session, will also look into this. What we cannot answer currently is whether there is a specific subgroup at risk for a suboptimal immune response. Therefore, we have formed a consortium to conduct a meta-analysis of different vaccination studies among patients with cancer and we will hopefully be able to answer this in the future. Furthermore, it will be essential to have a proper correlate of protection that is easy to measure. The initiative taken by the U.S. government is therefore very important.”
Perspective
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Marie von Lilienfeld-Toal, MD
First, COVID-19 vaccination appears as safe in [patients with cancer] as in otherwise healthy individuals. Possibly the most important result from the VOICE study 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.
In contrast, patients with hematologic malignancies have a diminished serologic response compared with patients with solid tumors. This does not appear to apply to all hematologic malignancies, although that finding is not completely robust yet.
We have also learned that the immunologic profile after vaccination resembles that after infection. The neutralizing capacity is possibly better after infection, but it is there in patients with cancer. Similar to the observation after vaccination, the serologic response does not always correlate with T cell response but sometimes T cells can be detected where the serologic response is missing, possibly suggesting some compensatory mechanism.
Longer follow-up of the present study should include more about the clinical efficacy and help us understand how this correlates with immunologic outcome parameters. We have reason to believe that the clinical efficacy is going to be high, but this is only an observation just looking at the rate of COVID-19 infections or death in patients on active cancer therapy who have been vaccinated. We also would like to know how long protection against COVID-19 lasts among patients with cancer, risk factors other than the cancer and subsequent treatment, what the underlying cause is in those with poor response to vaccination, and more aggregated data on the association between sex and age and efficacy and toxicity, as there appears to be a suggestion from current data that women fare worse than men in terms of vaccine efficacy.
To protect patients with cancer, everyone around the patient, as well as the community, needs to be vaccinated. We do not have data concerning the protective herd effect of COVID-19 vaccination, but the protective effect for patients with cancer is to be expected.
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Oosting SF, et al. Abstract LBA8. Presented at: European Society for Medical Oncology Congress (virtual meeting); Sept. 17-21, 2021.
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