Cytokine release syndrome-like serum responses after COVID-19 vaccination are frequent and clinically inapparent under cancer immunotherapy

Walle, Thomas; Bajaj, Sunanjay; Kraske, Joscha A.; Rosner, Thomas; Müller, Lisa; Strobel, Stefanie; Burghaus, Jana; Kallenberger, Stefan M.; Stein-Thöringer, Christoph; Jenzer, Maximilian; Schubert, Antje; Kahle, Steffen; Williams, Anja; Hoyler, Birgit; Zielske, Lin; Skatula, Renate; Sawall, Stefan; Leber, Mathias F.; Kunes, Russell; Krisam, Johannes; Schneeweiß, Andreas; Krauß, Jürgen; Apostolidis, Leonidas; Berger, Anne; Zschäbitz, Stefanie; Springfeld, Christoph; Cussigh, Christiane S.; Kälber, Katharina A.; Abdelrahim, Omar; Busch, Elena; Derigs, Patrick; Dischinger, Katharina; Mitri, Fouad; Schmidt, Kerstin; Bhatti, Irfan A.; Grün, B.; Hohmann, Nicolas; Woydack, Lena; Zhang, Xinwen; Ferber, Dyke; Möck, Andreas; Pompecki, Tillmann; Schank, Timo; Fremd, Carlo; Haag, Georg Martin; Halama, Niels; Kirsten, Romy; Hassel, Jessica C.; Jäger, Dirk; Ungerechts, Guy

doi:10.1038/s43018-022-00398-7

Cited by 14 publications

(11 citation statements)

References 34 publications

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“…Additionally, we investigated whether CCG responses are different in patients who developed severe AE: only placental growth factor (PlGF) was observed to be significantly downregulated after the primer dose in an uncorrected paired t-test statistics ( p = 0.027) and was not significant after post-hoc false discovery rate correction. These data fit well with studies suggesting that systemic adverse events noted after vaccination in cancer patients are not necessarily vaccine related [5, 28].…”

Section: Resultssupporting

confidence: 89%

Predictive model for BNT162b2 vaccine response in cancer patients based on cytokines and growth factors

Konnova

Winter

Gupta

et al. 2022

Preprint

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Background: Patients with cancer, especially haematological cancer, are at increased risk for breakthrough COVID-19 infection. However, so far, a predictive biomarker that can assess compromised vaccine-induced anti-SARS-CoV-2 immunity in cancer patients has not been proposed. Methods: Here, we employed machine learning approaches to identify a biomarker signature based on blood cytokine and growth factors linked to vaccine response from 199 cancer patients receiving BNT162b2 vaccine. Results: We show that C-reactive protein (CRP; general marker of inflammation), interleukin (IL)-15 (a pro-inflammatory cytokine), IL-18 (interferon-gamma inducing factor), and placental growth factor (an angiogenic cytokine) can correctly classify patients with a diminished vaccine response assessed at day 49 with >80% accuracy. Amongst these, CRP showed the highest predictive value for poor response to vaccine administration. Importantly, this unique signature of vaccine response was present at different studied timepoints both before and after vaccination and was not majorly affected by different anti-cancer treatments. Conclusion: While we propose a blood-based signature of cytokines and growth factors that can be employed in identifying cancer patients at continued risk of COVID-19, our data also importantly suggest that such a signature could reflect the inherent make-up of some cancer patients who are also refractive to immunotherapy.

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Section: Resultssupporting

confidence: 89%

Predictive model for BNT162b2 vaccine response in cancer patients based on cytokines and growth factors

Konnova

Winter

Gupta

et al. 2022

Preprint

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“…To the best of our knowledge, a higher prevalence of AEs in patients with long-standing disease or long duration of immunotherapy has not been reported, but this may reflect a more robust reaction of the immune system and cytokine production in patients with effectively activated T-cells. Cytokine-release syndrome-like serum responses have been recently reported in cancer patients under immunotherapy who have been vaccinated against SARS-CoV-2 [ 24 , 25 ].…”

Section: Discussionmentioning

confidence: 99%

Immunogenicity and Safety of the BNT162b2 mRNA COVID-19 Vaccine in Patients with Melanoma Treated with Immunotherapy

Diamantopoulos

Kontandreopoulou

Gkoufa

et al. 2022

Cancers

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The BNT162b2 vaccine against SARS-CoV-2 has a proven efficacy and a favorable safety profile. In cancer patients under immunotherapy in the form of immune-checkpoint inhibitors (ICIs), the efficacy of the vaccine has not been thoroughly studied, while a theoretical concern has also been raised about triggering immune-related adverse events (irAEs) by the vaccine. We conducted a prospective, non-interventional study on the immunogenicity and safety of the BNT162b2 vaccine in patients with advanced or metastatic melanoma treated with ICIs. Blood samples were obtained 0–4 days before the first dose and 12–21 days after the second dose of the vaccine for the quantification of the SARS-CoV-2 anti-spike antibody using an ELISA and immunophenotyping of the T and myeloid cell subpopulations. The active recording of AEs for a two-month period was conducted. Forty patients were included in the study. All but one (97.3%) achieved seroconversion after two doses of the vaccine and no correlations of the antibody titers with any of the studied parameters (age, gender, stage and duration of the disease, type of ICI, previous treatment, etc.) were found. Moreover, no differences in the subpopulations of the T cells (including the T-regulatory cells) or the myeloid cells were found pre- and post-vaccination. All AEs were low-grade, while one case of arthritis exacerbation was noted. The seroconversion rate in the studied population was high and was comparable to that of healthy subjects, while no major safety issues were raised during the safety follow-up. Finally, no derangements in the subpopulations of T cells or myeloid cells were noted. This is the first study focusing on the immunogenicity, safety, and effect of anti-SARS-CoV-2 vaccines on the blood-cell immunophenotype status of patients with melanoma treated with ICIs.

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“…Immunotherapies can enhance the immune response by reinvigorating exhausted T cells, and therefore may potentiate cell-mediated vaccine responses. Despite the amplified immune response with ICIs, patients rarely display symptoms of immunerelated adverse events (irAEs) or cytokine release syndrome (CRS), thus highlighting a favourable safety profile in this cohort [103]. Patients on endocrine or targeted therapies are unlikely to have treatment-driven reduced vaccine-induced immune responses [15][16][17]23].…”

Section: Anticancer Therapies Associated With Reduced Immunogenicity ...mentioning

confidence: 99%

Immunogenicity of SARS-CoV-2 vaccines in patients with cancer

Kakkassery

Carpenter

Patten

et al. 2022

Trends in Molecular Medicine

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Cytokine release syndrome-like serum responses after COVID-19 vaccination are frequent and clinically inapparent under cancer immunotherapy

Cited by 14 publications

References 34 publications

Predictive model for BNT162b2 vaccine response in cancer patients based on cytokines and growth factors

Predictive model for BNT162b2 vaccine response in cancer patients based on cytokines and growth factors

Immunogenicity and Safety of the BNT162b2 mRNA COVID-19 Vaccine in Patients with Melanoma Treated with Immunotherapy

Immunogenicity of SARS-CoV-2 vaccines in patients with cancer

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