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Rapid Response to Immune-Related Adverse Events Improves Patient Care

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Physicians within the Johns Hopkins Health System can now receive rapid advice from a multidisciplinary team of colleagues who have experience treating immune-related adverse events (AEs) that often follow the use of immune checkpoint inhibitors.

October 8, 2019

Among the 34 referring providers who used the team’s services and responded to a post-pilot survey, 100% used some (n=15) or all (n=19) of their recommendations, and 73.5% said the IR-tox team’s recommendations changed their diagnosis or management of an AE.

Something as simple as a listserv is helping to improve the care of Johns Hopkins patients with cancer. Physicians within the Johns Hopkins Health System can now receive rapid advice from a multidisciplinary team of colleagues who have experience treating immune-related adverse events (AEs) that often follow the use of immune checkpoint inhibitors. Referral requests are emailed to the team and answers are provided within 24 hours.

“Immune-related adverse events can affect every part of the body and can sometimes be challenging to diagnose since onset and duration of symptoms vary greatly,” says Laura Cappelli, a rheumatologist and assistant professor of medicine. “Having a team of specialists at the ready allows us to provide more rapid and effective care for patients and to balance their oncologic and rheumatologic needs.”

Currently, up to 43.6% of U.S. patients with cancer are eligible to be treated with immune checkpoint inhibitors (ipilimumab, pembrolizumab, nivolumab, avelumab, atezolizumab, durvalumab, cemiplimab), including those with melanoma and renal cell carcinoma. It is likely that hundreds of thousands of U.S. patients receive them each year. They act by blocking the negative regulation of T-cells, which supercharges T-cell activity against cancer cells — but also increases inflammation, harming tissues and organs throughout the body and causing immune-related AEs. 

According to Cappelli, the number of patients who experience these side effects is hard to pin down because many AEs go unrecognized as such. One estimate is that 15% to 50% of patients receiving immune checkpoint inhibitors develop an immune-related AE. “The range is wide in part because drug regimens differ,” she says. “Combination therapies, for example, are known to trigger more AEs.”

AEs most commonly involve the skin, liver, gastrointestinal tract and endocrine glands, but the full list is quite long, including pneumonitis, vitiligo, type 1 diabetes, neuropathy, inflammatory arthritis and myositis. The broad spectrum of affected tissues makes multidisciplinary collaboration a must.

About two years ago, Cappelli and Jarushka Naidoo, assistant professor of oncology, teamed up to pilot a virtual immune-related toxicity (IR-tox) team to improve communication among relevant doctors at Johns Hopkins. The team was composed of 33 members, including eight medical oncologists, four oncology nurses and four rheumatologists, plus subspecialists in pulmonology, gastroenterology, neurology, endocrinology, dermatology, ophthalmology, cardiology, infectious diseases and hematology.

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Laura Cappelli

Emailed referrals follow a template and go to a core group of members on the team. One of them reviews the case and loops in relevant specialists (e.g., a cardiologist for suspected myocarditis). Input is then collected and sent back within a day.

For eight months, they collected data on their activities. Their results were published in June in the Journal of the National Comprehensive Cancer Network. They received 117 relevant referrals concerning 102 patients being treated (inpatient or outpatient) at the three participating Johns Hopkins hospitals. In addition to questions regarding patients who had already taken immune checkpoint inhibitors, about 10% of the referrals concerned patients with known autoimmune diseases whose doctors wondered about starting them on the drugs. 

Among the 34 referring providers who used the team’s services and responded to a post-pilot survey, 100% used some (n=15) or all (n=19) of their recommendations, and 73.5% said the IR-tox team’s recommendations changed their diagnosis or management of an AE.

Cappelli tells of a recent case: a patient who had slowly worsening kidney function. “There were many possible explanations, but the nephrologist on our IR-tox team encouraged a kidney biopsy. The patient was found to have immune checkpoint inhibitor-related acute interstitial nephritis,” she says, “which was greatly improved by the addition of steroids.” 

“Our experiences and the feedback we received were very positive, so we decided to continue the work of the tox team,” says Cappelli. “It not only improved patient care in the short term, it fostered collaboration among providers and helped bring to light patterns and questions that need to be addressed by further research.”


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