Cytokine release syndrome-like serum responses after COVID-19 vaccination are frequent and clinically inapparent under cancer immunotherapy
Thomas Walle, Sunanjay Bajaj, Joscha A. Kraske, Thomas Rösner, Christiane S. Cussigh, Katharina A. Kälber, Lisa Müller, S Strobel, Jana Burghaus, Stefan M. Kallenberger, Christoph Stein-Thöringer, Maximilian Jenzer, Antonia Schubert, Steffen Kahle, Anja Williams, Birgit Hoyler, Lin Zielske, Renate Skatula, Stefanie Sawall, Mathias F. Leber, Russell Kunes, Johannes Krisam, Carlo Fremd, Andreas Schneeweiß, Jürgen Krauß, Leonidas Apostolidis, Anne Berger, Georg Martin Haag, Stefanie Zschäbitz, Niels Halama, Christoph Springfeld, Romy Kirsten, Jessica C. Hassel, Dirk Jäger, NCT ANTICIPATE Investigators, Christiane S. Cussigh, Katharina A. Kälber, Omar Abdelrahim, Elena Busch, Patrick Derigs, Katharina Dischinger, Fouad Mitri, Kerstin Schmidt, Irfan A. Bhatti, Barbara Grün, Nicolas Hohmann, Lena Woydack, Xinwen Zhang, Dyke Ferber, Andreas Möck, Tillmann Pompecki, Timo Schank, Carlo Fremd, Georg Martin Haag, Niels Halama, Romy Kirsten, Jessica C. Hassel, Dirk Jäger, Guy Ungerechts
Abstract
Patients with cancer frequently receive immune-checkpoint inhibitors (ICIs), which may modulate immune responses to COVID-19 vaccines. Recently, cytokine release syndrome (CRS) was observed in a patient with cancer who received BTN162b2 vaccination under ICI treatment. Here, we analyzed adverse events and serum cytokines in patients with 23 different tumors undergoing (n = 64) or not undergoing (n = 26) COVID-19 vaccination under ICI therapy in a prospectively planned German single-center cohort study (n = 220). We did not observe clinically relevant CRS (≥grade 2) after vaccination (95% CI 0-5.6%; Common Terminology of Adverse Events v.5.0) in this small cohort. Within 4 weeks after vaccination, serious adverse events occurred in eight patients (12.5% 95% CI 5.6-23%): six patients were hospitalized due to events common under cancer therapy including immune related adverse events and two patients died due to conditions present before vaccination. Despite absence of CRS symptoms, a set of pairwise-correlated CRS-associated cytokines, including CXCL8 and interleukin-6 was >1.5-fold upregulated in 40% (95% CI 23.9-57.9%) of patients after vaccination. Hence, elevated cytokine levels are common and not sufficient to establish CRS diagnosis.