Immunogenicity after second and third mRNA-1273 vaccination doses in patients receiving chemotherapy, immunotherapy, or both for solid tumours

Link to paper

Oosting SF, van der Veldt AAM, Fehrmann RSN, GeurtsvanKessel CH, van Binnendijk RS, Dingemans AC, Smit EF, Hiltermann TJN, den Hartog G, Jalving M, Westphal TT, Bhattacharya A, de Wilt F, Boersma A, M, van Zijl L, Rimmelzwaan GF, Kvistborg, van Els CACM, Rots NY, van Baarle D, Haanen JBAG, de Vries EGE

Patients with cancer are at an increased risk of severe COVID-19. Breakthrough infections after two vaccinations do occur and can be lethal.123 Most patients treated for a solid tumour develop an adequate humoral response against SARS-CoV-2 after two vaccinations; however, antibody concentrations tend to be lower when vaccinations are administered during chemotherapy, resulting in a suboptimal response in a small proportion of patients.45 In addition, binding and neutralising antibody concentrations decrease over time, resulting in a further decrease in immunity.6 This finding prompted many countries to prioritise these patients for a third vaccination. However, little information is available about the immunogenicity of a third vaccination in patients treated for solid tumours, especially against the currently most prevalent variant, omicron (B.1.1.529).78

In the VOICE trial, we previously reported on safety and humoral and cellular responses 28 days after the second mRNA-1273 (Moderna Biotech, Madrid, Spain) vaccination in patients with solid tumours while receiving immunotherapy (cohort B), chemotherapy (cohort C), or both (cohort D) compared with individuals without cancer (cohort A).5 Nine (7%) of 131 patients in cohort B, 37 (16%) of 229 patients in cohort C, 16 (11%) of 143 patients in cohort D, and one (<1%) of 240 patients in cohort A, classifying as inadequate responders (previously defined as a binding antibody concentration of ≤300 binding antibody units [BAU]/mL), were eligible to receive a third vaccination after a protocol amendment on Sept 10, 2021 (see appendix pp 4–5 for trial design and study disposition). At the time of the protocol amendment, the benefit of a third vaccination was not yet clear, and it was not standard policy in the Netherlands, where this study was done.

Here, we report follow-up data—namely, the secondary and exploratory immunogenicity endpoints at 6 months after the second vaccination, including SARS-CoV-2 spike S1-specific serum IgG (hereafter SARS-CoV-2-binding) antibody concentrations in the per-protocol population and, in a subgroup (appendix p 2), spike-specific T cells and virus neutralising antibodies against SARS-CoV-2 D614G (hereafter referred to as wild-type SARS-CoV-2) and against omicron, as previously described.9 Laboratory assessments, subgroup details, and cancer details can be found in the appendix (pp 2–3). Furthermore, we report breakthrough infections and humoral and cellular responses 28 days after a third mRNA-1273 vaccination in initially inadequate responders and we provide information on safety.