European Urologists Release Position Paper on Immune Checkpoint Inhibitor Toxicities

By Marilynn Larkin

July 05, 2019

NEW YORK (Reuters Health) - The European Association of Urology (EAU) has issued a position paper on diagnosis and management of toxicities related to the use of immune checkpoint inhibitors (ICIs) in advanced cancer.

Dr. Marc-Oliver Grimm of Jena University Hospital in Germany summarized some key points of the paper, which was published online June 21 in European Urology, and the rationale for issuing it, in an email to Reuters Health.

"ICIs are approved for a rapidly increasing number of cancer indications, including urologic tumors like renal cell carcinoma and urothelial (e.g., bladder) cancer," he said. "ICIs do not attack the tumor directly (like chemotherapy, for example), but activate the immune system, which in turn becomes active against the respective cancer."

"However, harnessing the immune system sometimes leads to immune-related adverse events (irAEs)," he noted. "These most frequently affect the skin with exanthema and pruritus, liver with hepatitis, colon with diarrhea/colitis, lung with pneumonitis, and the endocrine system."

That said, "irAEs may occur in any organ system," he added. "The symptoms are frequently nonspecific, making their attribution difficult, and the differential diagnosis between irAEs and infection (e.g., pneumonitis vs. pneumonia) imponderable."

For ICIs to be used safely - a primary aim of the position paper - "it is critical that clinicians prescribing ICIs or supervising patients under or after ICI therapy are well trained to identify irAEs promptly, monitor patients adequately, and initiate early treatment, since delays might result in symptom worsening and further, sometimes severe complications," Dr. Grimm said. "Management of irAEs frequently includes temporary immunosuppression using high-dose corticosteroid treatment."

"Since early recognition and management of irAEs mitigates the risk for severe toxicity, the knowledge about immune-checkpoint inhibition summarized in the current EAU position paper should be delivered to other medical professionals (e.g., those involved in emergency care), too," he concluded.

Some additional points in the paper include:

- Detailed staging and consideration of previous treatments for advanced disease are essential for deciding on patient eligibility for ICI therapy.

- To identify irAEs as early as possible, patients should be asked regularly about skin, bowel and/or pulmonary symptoms. Regular laboratory analyses should include liver and pancreas enzymes as well as creatinine. Thyroid-stimulating hormone should be closely monitored to identify hypo- or hyperthyroidism.

- ICIs are not recommended for prostate cancer outside of clinical trials.

Dr. David Wise, a medical oncologist at NYU Langone's Perlmutter Cancer Center, commented by email, "Checkpoint immunotherapy has rapidly emerged as one of the most broadly effective anti-cancer therapies. The treatment paradigm for urologic cancers has quickly shifted due to the incorporation of checkpoint immunotherapies as standard and investigational treatment options."

"Multidisciplinary cohesiveness is absolutely necessary in the care of patients treated with checkpoint immunotherapy," he told Reuters Health. "This will become increasingly important as immunotherapy is used in earlier stages of urologic disease."

"An in-depth understanding of the unique mode of action, response pattern, and toxicity profile of checkpoint immunotherapy is vital to any physician who treats urologic cancer," he concluded.


European Urology 2019.