Cytokine release syndrome-like serum responses after COVID-19 vaccination are frequent but clinically inapparent in cancer patients under immune checkpoint therapy

Walle, Thomas; Bajaj, Sunanjay; Kraske, Joscha A.; Rosner, Thomas; Cussigh, Christiane S.; Kälber, Katharina A.; 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; Fremd, Carlo; Schneeweiß, Andreas; Krauß, Jürgen; Berger, Anne; Haag, Georg Martin; Zschäbitz, Stefanie; Halama, Niels; Springfeld, Christoph; Kirsten, Romy; Hassel, Jessica C.; Jäger, Dirk; Ungerechts, Guy

doi:10.1101/2021.12.08.21267430

Cited by 5 publications

(3 citation statements)

References 27 publications

(40 reference statements)

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“…Vaccine efficacy in patients treated with immune checkpoint inhibitors (ICIs) appears to be comparable to that observed in healthy individuals, although questions surrounding an altered risk of immune related adverse events (irAEs) after vaccination have been posed [16][17][18]. In particular, the possibility of aberrant cytokine production with elevated IL-2, IL-6, CXCL8, CCL2, and sIL-1R, after SARS-CoV-2 vaccination in patients receiving ICIs has only recently emerged in preliminary reports [19,20]. Further, while autoantibody development has been correlated with irAEs in patients receiving IO treatment, whether SARS-CoV-2 vaccination can affect autoantibody generation is entirely unknown [21,22].…”

Section: Introductionmentioning

confidence: 99%

Longitudinal efficacy and toxicity of SARS-CoV-2 vaccination in cancer patients treated with immunotherapy

et al. 2023

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Despite more than 2 years having elapsed since the onset of SARS-CoV-2 pandemic, a level of hesitation around increased SARS-CoV-2 vaccine toxicity in cancer patients receiving immunotherapy (IO) remains. This hesitation stems from the idea that IO agents could elicit an overwhelming immune stimulation post vaccination and therefore increase the risk of vaccine-related toxicity. The aim of our study was to explore serological responses to SARS-CoV-2 vaccination in patients treated with IO and describe the level of immune stimulation using parameters such as blood cytokines, autoantibody levels and immune related adverse events (irAEs) post vaccination. Fifty-one evaluable patients were enrolled in this longitudinal study. Absolute levels and neutralization potential of anti-SARS-CoV-2 antibodies were not significantly different in the IO group compared to non-IO. Chemotherapy adversely affected seroconversion when compared to IO and/or targeted treatment. Following vaccination, the prevalence of grade ≥2 irAEs in patients treated with IO was not higher than the usual reported IO toxicity. We report, for the first time, that anti-SARS-CoV-2 vaccination, elicited the generation of five autoantibodies. The significantly increased autoantibodies were IgM autoantibodies against beta-2 glycoprotein (p = 0.02), myeloperoxidase (p = 0.03), nucleosome (p = 0.041), SPLUNC2 (p < 0.001) and IgG autoantibody against Myosin Heavy Chain 6 (MYH6) (p < 0.001). Overall, comprehensive analysis of a small cohort showed that co-administration of SARS-CoV-2 vaccine and IO is not associated with increased irAEs. Nevertheless, the detection of autoantibodies post anti-SARS-CoV-2 vaccination warrants further investigation (NCT03702309).

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Section: Introductionmentioning

confidence: 99%

Longitudinal efficacy and toxicity of SARS-CoV-2 vaccination in cancer patients treated with immunotherapy

et al. 2023

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“…Importantly, transient increases in IL-15 and IFN-g levels were also identified as biomarkers for anti-SARS-CoV-2 responses in a healthy population (12). However, none of these biomarkers are currently available for cancer patients, where such a marker can distinguish subgroups of patients which are poorly protected by SARS-CoV-2 vaccination and remain in need of additional (preventive) options (14)(15)(16). CCGs are not only important in the regulation of inflammation occurring in viral infections such as SARS-CoV-2 (12,(17)(18)(19) and influenza (20,21), but also play an important role in the initiation and progression of cancers (22)(23)(24)(25).…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2022

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BackgroundPatients with cancer, especially hematological cancer, are at increased risk for breakthrough COVID-19 infection. So far, a predictive biomarker that can assess compromised vaccine-induced anti-SARS-CoV-2 immunity in cancer patients has not been proposed.MethodsWe employed machine learning approaches to identify a biomarker signature based on blood cytokines, chemokines, and immune- and non-immune-related growth factors linked to vaccine immunogenicity in 199 cancer patients receiving the BNT162b2 vaccine.ResultsC-reactive protein (general marker of inflammation), interleukin (IL)-15 (a pro-inflammatory cytokine), IL-18 (interferon-gamma inducing factor), and placental growth factor (an angiogenic cytokine) correctly classified 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.ConclusionWe propose a blood-based signature of cytokines and growth factors that can be employed in identifying cancer patients at persistent high risk of COVID-19 despite vaccination with BNT162b2. Our data also suggest that such a signature may reflect the inherent immunological constitution of some cancer patients who are refractive to immunotherapy.

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“…Vaccine e cacy in patients treated with immune checkpoint inhibitors (ICIs) appears to be comparable to that observed in healthy individuals, although questions surrounding an altered risk of immune-related adverse events (irAEs) after vaccination have been posed (16)(17)(18). In particular, the possibility of aberrant cytokine production with elevated IL-2, IL-6, CXCL8, CCL2, and sIL-1R, after SARS-CoV-2 vaccination in patients receiving ICIs has only recently emerged in preliminary reports (19,20). Further, while autoantibody development has been correlated with irAEs in patients receiving IO treatment, whether SARS-CoV-2 vaccination can affect autoantibody generation is entirely unknown (21,22).…”

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confidence: 99%

Longitudinal efficacy and toxicity of SARS-CoV-2 vaccination in cancer patients treated with immunotherapy

Spiliopoulou

Rensburg

Avery

et al. 2022

Preprint

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Background Despite more than 2 years having elapsed since the onset of SARS-CoV-2 pandemic, a level of hesitation around increased SARS-CoV-2 vaccine toxicity in cancer patients receiving immunotherapy (IO) remains. Here, we explore serological responses to SARS-CoV-2 vaccination in patients treated with IO and we describe blood cytokines, autoantibody levels and immune-related adverse events (irAEs) post vaccination. Methods Serum anti-SARS-CoV-2 spike (S) protein receptor binding domain (RBD) antibodies, surrogate viral neutralization test (sVNT), Th1/Th2 cytokines and antibodies against self-antigens were quantified at baseline, between 1st and 2nd vaccine doses, at 1 week (1W), 1 month (1M), 4–6 months and 10–12 months after the 2nd dose. Grade 2 or higher (≥ gr2+) irAEs were captured prospectively. Results Fifty-one evaluable patients were enrolled in this longitudinal study, 35 on immunotherapy (IO) and 16 on non-immunotherapy (non-IO) treatment. Absolute levels and neutralization potential of anti-SARS-CoV-2 antibodies were not significantly different in the IO group compared to non-IO. Chemotherapy adversely affects seroconversion when compared to IO and/or targeted treatment with antibody levels of 67.6 U/mL vs 1441 U/mL (p = 0.006) and sVNT of 70.9% vs 94.5% (p = 0.009), at 1M after 2nd vaccine dose. Following vaccination, the prevalence of grade ≥ 2 irAEs in patients treated with IO was not higher than the usual reported IO toxicity. We report, for the first time, that post-vaccination, IgM autoantibodies against beta 2 glycoprotein (p = 0.02), myeloperoxidase (p = 0.03), nucleosome (p = 0.041), SPLUNC2 (p < 0.001) and IgG autoantibody against Myosin Heavy Chain 6 (MYH6) (p < 0.001), were significantly elevated and this increase was unrelated to the type of treatment. Discussion Comprehensive analysis of a small cohort showed that co-administration of SARS-CoV-2 vaccine and IO is not associated with increased irAEs. The detection of autoantibodies post anti-SARS-CoV-2 vaccination warrants further investigation. (NCT03702309)

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Cytokine release syndrome-like serum responses after COVID-19 vaccination are frequent but clinically inapparent in cancer patients under immune checkpoint therapy

Cited by 5 publications

References 27 publications

Longitudinal efficacy and toxicity of SARS-CoV-2 vaccination in cancer patients treated with immunotherapy

Longitudinal efficacy and toxicity of SARS-CoV-2 vaccination in cancer patients treated with immunotherapy

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

Longitudinal efficacy and toxicity of SARS-CoV-2 vaccination in cancer patients treated with immunotherapy

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