Factors associated with long-term antibody response after COVID-19 vaccination in patients treated with systemic treatment for solid tumors.

Treatment with chemotherapy and immunotherapy at the time of COVID-19 vaccination may result in inadequate humoral responses.1Peeters M. Verbruggen L. Teuwen L. et al.Reduced humoral immune response after BNT162b2 coronavirus disease 2019 messenger RNA vaccination in cancer patients under antineoplastic treatment.ESMO Open. 2021; 6100274Abstract Full Text Full Text PDF Scopus (49) Google Scholar,2Oosting S.F. van der Veldt A.A.M. GeurtsvanKessel C.H. et al.mRNA-1273 COVID-19 vaccination in patients receiving chemotherapy, immunotherapy, or chemoimmunotherapy for solid tumours: a prospective, multicentre, non-inferiority trial.Lancet Oncol. 2021; 22: 1681-1691Abstract Full Text Full Text PDF PubMed Scopus (72) Google Scholar We and others demonstrated that a third vaccination increases serum SARS-CoV-2 specific antibody concentration, but little is known about long-term antibody concentrations and breakthrough infections in these patients.3Oosting S.F. van der Veldt A.A.M. Fehrmann R.S.N. et al.Immunogenicity after second and third mRNA-1273 vaccination doses in patients receiving chemotherapy, immunotherapy, or both for solid tumours.Lancet Oncol. 2022; 23: 833-835Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar, 4Fendler A. Shephers S.T.C. Au L. et al.Immune responses following third COVID-19 vaccination are reduced in patients with hematological malignancies compared to patients with solid cancer.Cancer Cell. 2022; 40: 438Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar, 5Ehmsen S. Asmussen A. Jeppesen S.S. et al.Antibody responses following third mRNA COVID-19 vaccination in patients with cancer and potential timing of a fourth vaccination.Cancer Cell. 2022; 40: 338-339Abstract Full Text Full Text PDF PubMed Scopus (15) Google Scholar Here, we report the 18-month data of the prospective multicenter VOICE trial (Figure S1, NCT04715438) of COVID-19 vaccination in patients treated for solid tumors with immunotherapy (cohort B), chemotherapy (cohort C), or chemoimmunotherapy (cohort D) compared to controls (cohort A). In the trial, participants received two mRNA-1273 vaccinations (100 μg intramuscularly) four weeks apart and a third vaccination if the initial response was inadequate. All participants had access to additional COVID-19 mRNA vaccinations in the national vaccination program. SARS-CoV-2-binding antibody concentrations were measured as previously described.2Oosting S.F. van der Veldt A.A.M. GeurtsvanKessel C.H. et al.mRNA-1273 COVID-19 vaccination in patients receiving chemotherapy, immunotherapy, or chemoimmunotherapy for solid tumours: a prospective, multicentre, non-inferiority trial.Lancet Oncol. 2021; 22: 1681-1691Abstract Full Text Full Text PDF PubMed Scopus (72) Google Scholar Breakthrough infections were assessed with 3-monthly questionnaires and with SARS-CoV-2 nucleoprotein-specific IgG antibody measurements. At 18 months, 112, 68, 97, and 36 participants were evaluable in cohorts A, B, C, and D, respectively (Figure S2). Participants received up to six vaccinations in total (Table S1). The high levels of binding antibody concentrations at one year were maintained at 18 months in all cohorts (Figure S3), and the geometric mean concentrations even slightly increased by 1.22, 1.53, 1.23, and 1.03 fold in cohorts A, B, C, and D, respectively. A SARS-CoV-2 infection in the previous 6 months was reported by 16.1% (n=18), 8.8% (n=6), 16.5% (n=16), and 8.3% (n=3) in cohorts A, B, C, and D (Table S2) and serological evidence of prior SARS-CoV-2 infection at 18 months was found in 26.8% (n=30), 17.6% (n=12), 21.7% (n=21), and 11.1% (n=4). Decision tree analysis identified the absence of serological evidence of a prior infection as the most important factor for lower SARS-CoV-2-binding antibody concentrations at 18 months. Other determinants were long interval since last vaccination, no prior infection based on questionnaires, and long interval since infection (Figure 1, S4). An increase in antibody concentration compared to previous measurement at one year was associated with a prior infection based on serology and time since last vaccination (Figure S5). Based on serology and the questionnaire, 121 participants did not have breakthrough infections nor had received additional vaccines in the last six months. The median reduction of SARS-CoV-2-binding antibody concentration from one year to 18 months in these 121 participants was 1618.2 BAU/ml. The geometric mean concentrations for these participants were 3571.3, 3394.1, 4188.3, and 1607.4 BAU/ml in cohorts A, B, C, and D, respectively at 18 months, compared to 5243, 3373, 6334, and 3055.7, respectively at one year. Our 18-month data show that patients treated with chemotherapy, immunotherapy, or chemoimmunotherapy for a solid tumor at the time of initial vaccination have sustained high SARS-CoV-2-binding antibody concentrations, similar to controls. Additional vaccinations and infections but not cancer treatment determine antibody response over time. These encouraging results can be used to develop future vaccination strategies for patients with solid tumors, not only for prevention of infectious diseases but also for the development of cancer vaccines. Download .docx (1.32 MB) Help with docx files