One-year data on immunogenicity and breakthrough infections in patients with solid tumors vaccinated against COVID-19 during systemic cancer treatment

Veldt, Astrid A.M. van der; Oosting, Sjoukje F.; Fehrmann, Rudolf S.N.; GeurtsvanKessel, Corine H.; Binnendijk, Rob van; Dingemans, A.-M.C.; Smit, Egbert F.; Hiltermann, T. Jeroen N.; Hartog, Gerco den; Jalving, Mathilde; Westphal, Tatjana T; Bhattacharya, Arkajyoti; Wilt, Faye de; Ernst, Sophie M.; Boerma, Annemarie; Zijl, L. van; Rimmelzwaan, Guus F.; Kvistborg, Pia; van, Cécile A. C. M.; Rots, Nynke Y.; Baarle, Debbie van; Haanen, John B.A.G.; Vries, Elisabeth G.E. de

doi:10.1016/j.esmoop.2023.100785

Cited by 2 publications

(1 citation statement)

References 4 publications

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“…In addition, mild SARS-CoV-2 infections and restraining measures may disrupt the regularity of antineoplastic treatment, leading to a potentially worsening effect on survival outcomes [16]. Limited data are also available about the capabilities of antibody responses induced by booster vaccinations in preventing breakthrough infections over the long term [17,18]. Here, we analyzed the incidence of SARS-CoV-2 infections in a prospective cohort of cancer patients with actively treated advanced disease who had participated in the Vax-On-Third study.…”

Section: Introductionmentioning

confidence: 99%

Effects of Antibody Response after Booster Vaccination on SARS-CoV-2 Breakthrough Infections and Disease Outcomes in Advanced Cancer Patients: A Prospective Analysis of the Vax-on-Third Study

et al. 2023

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(1) Background: The clinical implications of COVID-19 outbreaks following SARS-CoV-2 vaccination in immunocompromised recipients are a worldwide concern. Cancer patients on active treatment remain at an increased risk of developing breakthrough infections because of waning immunity and the emergence of SARS-CoV-2 variants. There is a paucity of data on the effects of COVID-19 outbreaks on long-term survival outcomes in this population. (2) Methods: We enrolled 230 cancer patients who were on active treatment for advanced disease and had received booster dosing of an mRNA-BNT162b2 vaccine as part of the Vax-On-Third trial between September 2021 and October 2021. Four weeks after the third immunization, IgG antibodies against the spike receptor domain of SARS-CoV-2 were tested in all patients. We prospectively evaluated the incidence of breakthrough infections and disease outcomes. The coprimary endpoints were the effects of antibody titers on the development of breakthrough infections and the impact of COVID-19 outbreaks on cancer treatment failure. (3) Results: At a median follow-up of 16.3 months (95% CI 14.5–17.0), 85 (37%) patients developed SARS-CoV-2 infection. Hospitalization was required in 11 patients (12.9%) and only 2 (2.3%) deaths related to COVID-19 outbreaks were observed. Median antibody titers were significantly lower in breakthrough cases than in non-cases (291 BAU/mL (95% CI 210–505) vs. 2798 BAU/mL (95% CI 2323–3613), p < 0.001). A serological titer cut-off below 803 BAU/mL was predictive of breakthrough infection. In multivariate testing, antibody titers and cytotoxic chemotherapy were independently associated with an increased risk of outbreaks. Time-to-treatment failure after booster dosing was significantly shorter in patients who contracted SARS-CoV-2 infection (3.1 months (95% CI 2.3–3.6) vs. 16.2 months (95% CI 14.3–17.0), p < 0.001) and had an antibody level below the cut-off (3.6 months (95% CI 3.0–4.5) vs. 14.6 months (95% CI 11.9–16.3), p < 0.001). A multivariate Cox regression model confirmed that both covariates independently had a worsening effect on time-to-treatment failure. (4) Conclusions: These data support the role of vaccine boosters in preventing the incidence and severity of COVID-19 outbreaks. Enhanced humoral immunity after the third vaccination significantly correlates with protection against breakthrough infections. Strategies aimed at restraining SARS-CoV-2 transmission in advanced cancer patients undergoing active treatment should be prioritized to mitigate the impact on disease outcomes.

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Section: Introductionmentioning

confidence: 99%

Effects of Antibody Response after Booster Vaccination on SARS-CoV-2 Breakthrough Infections and Disease Outcomes in Advanced Cancer Patients: A Prospective Analysis of the Vax-on-Third Study

et al. 2023

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mRNA-1273 vaccination induces polyfunctional memory CD4 and CD8 T cell responses in patients with solid cancers undergoing immunotherapy or/and chemotherapy

Gangaev,

van Sleen,

Brandhorst

et al. 2024

Front. Immunol.

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IntroductionResearch has confirmed the safety and comparable seroconversion rates following SARS-CoV-2 vaccination in patients with solid cancers. However, the impact of cancer treatment on vaccine-induced T cell responses remains poorly understood.MethodsIn this study, we expand on previous findings within the VOICE trial by evaluating the functional and phenotypic composition of mRNA-1273-induced T cell responses in patients with solid tumors undergoing immunotherapy, chemotherapy, or both, compared to individuals without cancer. We conducted an ELISpot analysis on 386 participants to assess spike-specific T cell responses 28 days after full vaccination. Further in-depth characterization of using flow cytometry was performed on a subset of 63 participants to analyze the functional phenotype and differentiation state of spike-specific T cell responses.ResultsELISpot analysis showed robust induction of spike-specific T cell responses across all treatment groups, with response rates ranging from 75% to 80%. Flow cytometry analysis revealed a distinctive cytokine production pattern across cohorts, with CD4 T cells producing IFNγ, TNF, and IL-2, and CD8 T cells producing IFNγ, TNF, and CCL4. Variations were observed in the proportion of monofunctional CD4 T cells producing TNF, particularly higher in individuals without cancer and patients treated with chemotherapy alone, while those treated with immunotherapy or chemoimmunotherapy predominantly produced IFNγ. Despite these differences, polyfunctional spike-specific memory CD4 and CD8 T cell responses were comparable across cohorts. Notably, immunotherapy-treated patients exhibited an expansion of spike-specific CD4 T cells with a terminally differentiated effector memory phenotype.DiscussionThese findings demonstrate that systemic treatment in patients with solid tumors does not compromise the quality of polyfunctional mRNA-1273-induced T cell responses. This underscores the importance of COVID-19 vaccination in patients with solid cancers undergoing systemic treatment.

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One-year data on immunogenicity and breakthrough infections in patients with solid tumors vaccinated against COVID-19 during systemic cancer treatment

Cited by 2 publications

References 4 publications

Effects of Antibody Response after Booster Vaccination on SARS-CoV-2 Breakthrough Infections and Disease Outcomes in Advanced Cancer Patients: A Prospective Analysis of the Vax-on-Third Study

Effects of Antibody Response after Booster Vaccination on SARS-CoV-2 Breakthrough Infections and Disease Outcomes in Advanced Cancer Patients: A Prospective Analysis of the Vax-on-Third Study

mRNA-1273 vaccination induces polyfunctional memory CD4 and CD8 T cell responses in patients with solid cancers undergoing immunotherapy or/and chemotherapy

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