Immunotherapy as an advance in cancer medicine

– new and early detection method for side effects on the heart muscle.

Novel immunotherapies with “checkpoint inhibitors” (immune checkpoint inhibitors (ICI)) have revolutionized the treatment of cancer in recent years and led to improved therapy results. The therapy is designed to “unleash” the patient’s own immune system so that cancer cells can be better recognized and attacked. A study by an interdisciplinary group of researchers at Bonn University Hospital (UKB) has shown that the novel cancer therapy can subclinically affect the heart muscle to a previously unknown extent. The results of the prospective cardiac MRI study have been published in the renowned journal Radiology.

The main focus of the study was the occurrence of myocarditis under ICI therapy. This can (initially) be asymptomatic and subclinical – i.e. not noticeable to the patient. In rare cases, however, a fulminant, i.e. very rapid and severe, course may be present. Until now, it was unknown to what extent ICI therapy leads to inflammatory changes in the myocardium even in asymptomatic patients. In particular, MRI-specific inflammatory markers of the myocardium were elevated and signs of systolic dysfunction (impairment of cardiac deformation) were present in study participants after initiation of ICI therapy for cancer treatment.

Normally, the so-called immune checkpoints prevent an excessive reaction of the immune system (so-called autoimmune reaction) against the body’s own healthy cells. Some tumors specifically activate such immune checkpoints, so that immune cells that could actually recognize and fight the tumor are severely weakened. In ICI therapy, so-called checkpoint inhibitors or immune checkpoint inhibitors counteract this: they prevent the suppression of the immune response and thus cause the immune system to better recognize the tumor and attack it more intensively.

Changes in heart muscle tissue

The aim of the study was to investigate the extent to which ICI treatment causes changes in the heart muscle that can be detected using modern cardiac MRI techniques, such as inflammation, fibrosis (pathological proliferation of connective tissue) or functional disorders of the heart. In this study, for the first time, cancer patients scheduled for ICI therapy were evaluated with highly sensitive quantitative cardiac MRI techniques immediately before and 3 months after initiation of ICI therapy. ICI therapy was the only cancer treatment used during the study period. The results are expected to contribute to the early detection of serious side effects associated with immunotherapy, with the potential to prevent them in a timely manner.

“Using highly sensitive MRI markers, we were able to detect changes in the heart muscle tissue of the study participants, which indicate an inflammatory co-reaction in the context of the therapy,” explains PD Dr. Anton Faron. The physician is a specialist at the Clinic for Diagnostic and Interventional Radiology at Bonn University Hospital (UKB). Interestingly, these changes proceeded without accompanying symptoms in most patients. “This observation shows us that with cardiac MRI we have an important tool in our hands that can help, for example, to detect possible therapy side effects at an early stage and thus to be able to control therapies better and more precisely,” Faron emphasizes.

Study may open up opportunity to more accurately guide therapies

ICI-related myocarditis is a rare but potentially serious side effect that is most likely to occur within the first 3 months of treatment initiation. Therefore, the results have important implications for clinical practice and future research.

High-sensitivity MRI techniques make a significant contribution. They offer the possibility of advanced tissue characterization: “We were able to show that diffuse inflammation can be detected just with the modern quantitative MRI techniques. This has a direct relevance, also for the detection of severe courses of ICI-associated myocarditis in symptomatic patients,” explains PD Dr. Julian Luetkens. He is in charge of cardiac MRI diagnostics and, with the QILaB (Quantitative Imaging Lab Bonn), also heads a working group at the University Hospital Bonn that is involved in the development and use of innovative quantitative methods in MRI.

The interdisciplinary study at Bonn University Hospital involved its Clinic for Diagnostic and Interventional Radiology, the Medical Clinic and Polyclinic III of Internal Medicine, and the Clinic and Polyclinic for Dermatology and Allergology.

Publication: Anton Faron, MD* • Alexander Isaak, MD* • Narine Mesropyan, MD • Matthäus Reinert, MD • Katjana Schwab, MD • Judith Sirokay, MD • Alois M. Sprinkart, MD • Franz-Georg Bauernfeind, MD • Darius Dabir, MD • Claus C. Pieper, MD • Ann-Kristin Heine, MD • Daniel Kuetting, MD • Ulrike Attenberger, MD • Jennifer Landsberg, MD • Julian A. Luetkens, MD
https://pubs.rsna.org/doi/pdf/10.1148/radiol.2021210814

Press Contact:
Elke Pfeifer
Press spokeswoman and Head of Communications and Media, Bonn University Hospital (UKB)
Tel.: +49 (0)228 287-13457
E-Mail: elke.pfeifer@ukbonn.de

About Bonn University Hospital:
The Bonn University Hospital n (UKB) cares for over 400,000 patients* per year, employs 8,300 people and has a balance sheet total of over 1.3 billion euros. In addition to the more than 3,300 medical and dental students, around 600 young people are trained in other healthcare professions each year. The UKB is ranked first among university hospitals in NRW in the science ranking, has the fourth-highest case mix index in Germany, and in 2020 had the most economically successful annual result of all 35 German UKs and the only positive annual balance sheet of all UKs in NRW.

Wissenschaftliche Ansprechpartner:

Contact:
PD Dr. med. Julian A. Luetkens
Clinic for Diagnostic and Interventional Radiology, Bonn University Hospital (UKB)
Tel.: +49 (0)228 287-11831
E-Mail: julian.luetkens@ukbonn.de

Originalpublikation:

Publication: Anton Faron, MD* • Alexander Isaak, MD* • Narine Mesropyan, MD • Matthäus Reinert, MD • Katjana Schwab, MD • Judith Sirokay, MD • Alois M. Sprinkart, MD • Franz-Georg Bauernfeind, MD • Darius Dabir, MD • Claus C. Pieper, MD • Ann-Kristin Heine, MD • Daniel Kuetting, MD • Ulrike Attenberger, MD • Jennifer Landsberg, MD • Julian A. Luetkens, MD
https://pubs.rsna.org/doi/pdf/10.1148/radiol.2021210814

www.ukbonn.de