Does COVID-19 vaccination increase the risk of cancer patients undergoing therapy with immune checkpoint inhibitors to suffer a dangerous immune complication known as a "cytokine release syndrome"? A team of Heidelberg physicians and scientists has now shown in a clinical study: Increased serum levels of the characteristic cytokines occur frequently in cancer patients, but clinically relevant cases of the dreaded syndrome were not observed. The result supports the current recommendation to vaccinate cancer patients against COVID-19, even under therapy with immune checkpoint inhibitors.
Joint press release from the National Center for Tumor Diseases (NCT) Heidelberg, the German Cancer Research Center (DKFZ), Heidelberg University Hospital (UKHD), and the German Cancer Consortium (DKTK).
According to the German Robert Koch Institute, cancer patients are considered a risk group for severe courses of COVID-19 disease. For this reason, many patients consider it particularly important to protect themselves against the viral disease with a vaccination against COVID-19.
But is the Corona vaccination associated with special risks for people with cancer? Today, more and more cancer patients are being treated with a so-called "immune checkpoint inhibitor", often shortened to "immunotherapy". Immune checkpoint inhibitors block signals that cancer uses to slow down the immune system's T cells. The agents release the brakes on the immune system, reactivating the immune response against tumor cells.
"There was concern that immune checkpoint inhibitors could trigger strong, uncontrolled immune responses in vaccinated individuals," says Guy Ungerechts, senior physician in the Department of Medical Oncology at Heidelberg University Hospital and National Center for Tumor Diseases (NCT) in Heidelberg, Germany, and head of the Virotherapy Clinical Cooperation Unit at the German Cancer Research Center (DKFZ) and Heidelberg University Hospital (UKHD). Excessively activated T cells can trigger a dreaded cytokine release syndrome (CRS). This complication, which manifests itself with high fever, falling blood pressure, oxygen deficiency and, in extreme cases, multi-organ failure, can occur when activated immune cells release large quantities of messenger substances called cytokines.
"In order to provide the best possible advice to our patients, we wanted to find out whether CRS actually occurs frequently after corona vaccination when treated with immune checkpoint inhibitors. In addition, we wanted to clarify whether the determination of CRS-associated cytokines in the blood could be an early indication of the development of clinically manifest CRS," explains Thomas Walle, the lead author of the current study, who is a physician at the NCT Heidelberg and conducts research in the department headed by Guy Ungerechts at the DKFZ and in the German Cancer Consortium (DKTK).
In a prospective study, the oncologists at the NCT Heidelberg examined 64 vaccinated and 26 unvaccinated cancer patients undergoing therapy with immune checkpoint inhibitors. The study participants suffered from 23 different types of cancer. From the first vaccine dose to four weeks after the second vaccination, patients were monitored for adverse events. None of the patients experienced clinically relevant CRS. Nevertheless, certain cytokines characteristically associated with CRS were elevated to approximately 1.5 times baseline levels in 40 percent of participants after vaccination.
"Under therapy with immune checkpoint inhibitors, COVID vaccination appears to frequently trigger the release of CRS-associated cytokines but rarely causes symptoms," says Sunanjay Bajaj. "Cytokine measurements alone are therefore unlikely to be useful in assessing the risk of CRS." The first author of the current study conducts research as a medical student in the collaborative unit led by Guy Ungerechts, as well as in the DKTK.
Among the vaccinated patients, physicians also observed improved overall survival, which could not be explained solely by higher COVID-19-related mortality among the unvaccinated. "Of course, our result needs to be validated by a study with a larger number of cases," Guy Ungerechts said. "But for now, our data support the current recommendation to cancer patients on immune checkpoint inhibitor therapy to take advantage of vaccination against COVID-19 to protect against severe courses of viral infection."
Publication:
Thomas Walle, Sunanjay Bajaj, Joscha A. Kraske, Thomas Rösner, Christiane S. Cussigh, Katharina A. Kälber, Lisa Jasmin Müller, Sophia Boyoung Strobel, Jana Burghaus, Stefan M. Kallenberger, Christoph K. Stein-Thöringer, Maximilian Jenzer, Antonia Schubert, Steffen Kahle, Anja Williams, Birgit Hoyler, Lin Zielske, Renate Skatula, Stefanie Sawall, Mathias F. Leber, Russell Z. Kunes, Johannes Krisam, Carlo Fremd, Andreas Schneeweiss, Jürgen Krauss, Leonidas Apostolidis, Anne Katrin Berger, Georg M. Haag, Stefanie Zschäbitz, Niels Halama, Christoph Springfeld, Romy Kirsten, Jessica C. Hassel, Dirk Jäger, NCT ANTICIPATE Investigators and Guy Ungerechts. Cytokine release syndrome-like serum responses after COVID-19 vaccination are frequent and clinically inapparent under cancer immunotherapy. Nature Cancer 2022, DOI: https://doi.org/10.1038/s43018-022-00398-7
Press contact:
Dr. Martin Staiger
National Center for Tumor Diseases Heidelberg (NCT)
Press and Public Relations
Im Neuenheimer Feld 460
69120 Heidelberg
Tel.: +49 6221 42-1755
E-mail: martin.staiger@nct-heidelberg.de
www.nct-heidelberg.de
Dr. Sibylle Kohlstädt
German Cancer Research Center (DKFZ)
Strategic Communication and Public Relations
Im Neuenheimer Feld 280
69120 Heidelberg
Tel.: +49 6221 42-2843
E-mail: s.kohlstaedt@dkfz.de
www.dkfz.de
Doris Rübsam-Brodkorb
Heidelberg University Hospital and Medical Faculty of the University of Heidelberg
Press and Public Relations
Im Neuenheimer Feld 672
69120 Heidelberg
Tel.: +49 6221 56-5052
E-mail: doris.ruebsam-brodkorb@med.uni-heidelberg.de
www.klinikum.uni-heidelberg.de
National Center for Tumor Diseases (NCT) Heidelberg
The National Center for Tumor Diseases (NCT) Heidelberg is a joint institution of the German Cancer Research Center (DKFZ), the Heidelberg University Hospital (UKHD), the Medical Faculty of the University of Heidelberg and the German Cancer Aid. The aim of the NCT is to transfer promising approaches from cancer research to the clinic as quickly as possible and thus to benefit the patients. This applies to diagnosis as well as treatment, follow-up care or prevention. The tumor outpatient clinic is the heart of the NCT. Here, the patients benefit from an individual therapy plan drawn up by interdisciplinary panels of experts, the so-called tumor boards. Participation in clinical studies opens up access to innovative therapies. The NCT is thus a trend-setting platform for transferring new research results from the laboratory to the clinic. The NCT cooperates with self-help groups and supports them in their work. The NCT Heidelberg has had a partner location in Dresden since 2015. The Hopp Children's Cancer Center (KiTZ) was founded in Heidelberg in 2017. The pediatric oncologists at the KiTZ work together with the NCT Heidelberg in joint structures.
German Cancer Research Center
The German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) with its more than 3,000 employees is the largest biomedical research institution in Germany. More than 1,300 scientists at the DKFZ investigate how cancer develops, identify cancer risk factors and search for new strategies to prevent people from developing cancer. They are developing new methods to diagnose tumors more precisely and treat cancer patients more successfully. The DKFZ's Cancer Information Service (KID) provides patients, interested citizens and experts with individual answers to all questions on cancer.
Jointly with partners from the university hospitals, the DKFZ operates the National Center for Tumor Diseases (NCT) in Heidelberg and Dresden, and the Hopp Children's Tumour Center KiTZ in Heidelberg. In the German Consortium for Translational Cancer Research (DKTK), one of the six German Centers for Health Research, the DKFZ maintains translational centers at seven university partner locations. NCT and DKTK sites combine excellent universtity medicine with the high-profile research of the DKFZ. They contribute to the endeavor of transferring promising approaches from cancer research to the clinic and thus improving the chances of cancer patients.
The DKFZ is 90 percent financed by the Federal Ministry of Education and Research and 10 percent by the state of Baden-Württemberg. The DKFZ is a member of the Helmholtz Association of German Research Centers.
Heidelberg University Hospital and Faculty of Medicine: Internationally Renowned Patient Care, Research and Teaching
Heidelberg University Hospital (Universitätsklinikum Heidelberg, UKHD) is one of the largest and most prestigious medical centers in Germany. The Medical Faculty of Heidelberg University (Medizinische Fakultät Heidelberg, MFHD) belongs to the internationally renowned biomedical research institutions in Europe. Both institutions have the common goal of developing new therapies and implementing them rapidly for patients. Heidelberg University Hospital and the Medical Faculty of Heidelberg University employs around 14.000 employees and is committed to providing trainings and qualifications. Every year, around 84,000 patients and more than 1.000.000 outpatient cases are treated in more than 50 clinical departments with almost 2000 beds.
Together with the German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) and the German Cancer Aid, the UKHD established the first National Center for Tumor Diseases (NCT) in Heidelberg. The goal is to provide care at the highest level as an oncology center of excellence and to rapidly transfer promising approaches from cancer research to the hospital. In addition, the UKHD operates in partnership with the DKFZ and the University of Heidelberg the Hopp Children’s Cancer center Heidelberg (KiTZ), a unique and nationally known therapy and research center for oncological and hematological diseases in children and adolescents.
The Heidelberg Curriculum Medicinale (HeiCuMed) is one of the top medical training programs in Germany. Currently, there are about 4,000 future physicians studying in Heidelberg.
German Consortium for Translational Cancer Research (DKTK)
The German Consortium for Translational Cancer Research (DKTK) is a joint, long-term initiative of the Federal Ministry of Education and Research (BMBF), the participating federal states and the German Cancer Research Center (DKFZ) and was founded as one of the six German Centers for Health Research (DZGs). In the DKTK, the German Cancer Research Center (DKFZ) as the core center connects long-term with university partner locations and clinics in Germany that are particularly well-known oncologically. Research institutions and clinics in Berlin, Dresden, Essen/Düsseldorf, Frankfurt/Mainz, Freiburg, Heidelberg, Munich and Tübingen cooperate with the DKFZ in order to create optimal conditions for cancer research close to the clinic. The consortium promotes interdisciplinary research topics at the interface between basic research and clinical practice, as well as clinical studies on innovative therapy and diagnostic procedures. Another focus is the development of research platforms to accelerate the use of personalized cancer therapies and to improve the diagnosis and prevention of cancer.