ONCAlert | 2018 SGO Annual Meeting on Women’s Cancer

Identifying and Managing Immune-Related Adverse Events

Jennifer Fink
Published Online: Feb 19,2018

Randy F. Sweis, MD
Checkpoint inhibition amplifies immune activity, allowing the immune system to detect and destroy cancer cells. But in some patients, this amplification of the immune system causes uncomfortable, and potentially lethal, adverse events (AEs). As checkpoint inhibition is increasingly being utilized beyond the scope of clinical trials, it’s essential that community-based oncologists and physicians learn how to quickly diagnose and treat immune-related adverse events (irAEs).

“If we catch these events early, we can typically manage them very successfully in the vast majority of cases,” said Randy F. Sweis, MD, an instructor of medicine at the University of Chicago Medicine. “When we look historically at events that were severe, or even life threatening, a lot of times those occur in a setting in which there were delayed interventions.”

Red-Flag Symptoms

The AEs of chemotherapy and radiation are so familiar to the general public that most people can rattle them off without hesitation. The possible AEs of checkpoint inhibition are not nearly as well known yet, which can be challenging because the diagnosis and management of irAEs is largely dependent on patient awareness.

“When patients get diagnosed with cancer and are treated with chemotherapy, they often know what to look for. Immunotherapy is very different,” Sweis said. “That’s why patient education may be the most critical component to the appropriate management of adverse events with immunotherapies.”

Currently there are 6 FDA-approved immune checkpoint inhibitors: ipilimumab (Yervoy; anti–CTLA-4), nivolumab (Opdivo; anti–PD-1), pembrolizumab (Keytruda; anti–PD-1), atezolizumab (Tecentriq; anti–PD-L1), avelumab (Bavencio; anti–PD-L1), and durvalumab (Imfinzi; anti–PD-L1).

Patients being treated with any of these monoclonal antibodies should be instructed to report the following red-flag symptoms to their medical team immediately:

• Diarrhea (more than 2 loose stools in 24 hours)
• Bloody diarrhea
• Fever greater than 100.5°F
• Profound fatigue
• Production of yellow or green sputum
• Shortness of breath
• Skin rash

These symptoms are the most obvious manifestations of 3 of the most common irAEs: colitis, pneumonitis, and dermatologic AEs. However, irAEs can affect any organ system, so patients and families should be instructed to report any symptom that seems unusual.

During the 2017 ESMO Immuno-Oncology Symposium that took place December 7-10 in Geneva, Switzerland, the European Society for Medical Oncology released a guide of immunotherapy AEs for patients, based on the ESMO Clinical Practice Guidelines for the management of toxicities from immunotherapy. 1,2 The guide stated that in addition to the symptoms mentioned above, patients should also look out for less common symptoms, including headache, confusion, muscle weakness, numbness, painful or swollen joints, tendency to bruise easily, and loss of vision.


“Whenever we start a patient on checkpoint inhibition, I always emphasize that we’d rather hear from you sooner than later,” said Jeffrey Weber, MD, PhD, deputy director of the Perlmutter Cancer Center and co-director of the Melanoma Research Program at NYU Langone Health in New York, New York. “We’d rather hear about something and decide it’s not worth worrying about than not hear from you and let it develop into a full-blown [adverse event].”

Some patients are hesitant to report AEs because they don’t want them to potentially interfere with their cancer treatment. Weber suggests ensuring that patients know that there is absolutely no benefit to “toughing it out.” To underscore the importance of reporting AEs, let patients know that early detection and treatment of irAEs is key to successful management.

“I’ve been treating patients with immunotherapy for at least 15 years, and the only treatment-related deaths I’ve ever seen came about because patients elected to wait to let us know [about adverse events],” Weber said. “The quicker you get to it, the better off you’re going to be. Once you let things progress beyond a certain point, you’re truly behind the 8 ball in terms of managing the toxicities.”



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Identifying and Managing Immune-Related Adverse Events
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