Physician Awareness of Immune-Related Adverse Events of Immune Checkpoint Inhibitors

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Ahmed Bilal Khalid Department of Internal Medicine, Indiana University School of Medicine, and

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Gerardo Calderon Department of Internal Medicine, Indiana University School of Medicine, and

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Shadia I. Jalal Indiana University Melvin and Bren Simon Comprehensive Cancer Center, Indianapolis, Indiana.

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Greg A. Durm Indiana University Melvin and Bren Simon Comprehensive Cancer Center, Indianapolis, Indiana.

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Background: Immune checkpoint inhibitors (ICIs) have been proven to be very effective in the treatment of multiple cancers. They have a unique side-effect profile distinct from conventional chemotherapy that can manifest as immune-related adverse events (irAEs). With expanding ICI use, clinicians will increasingly encounter irAEs, and thus adequate physician knowledge on their recognition and management is crucial. Methods: To assess physician knowledge of irAEs due to ICIs, an online survey was administered to resident physicians in internal medicine (IM), emergency medicine, and family medicine (FM), as well as to faculty physicians in IM and FM. Results: We sent the survey to 413 physicians and received responses from 155 (38%), of which 110 were residents and 45 were faculty. Pembrolizumab was identified as an ICI by 79% of physicians, nivolumab by 64%, and ipilimumab by 55%. Twenty-five percent incorrectly thought infliximab and adalimumab were ICIs. Most physicians (93%) were able to identify the gastrointestinal tract as an irAE site, whereas only 57% and 67% were able to identify cardiovascular and renal systems as irAE sites, respectively. A total of 59% believed steroids negatively affect efficacy of ICIs and should be used with caution to treat irAEs, 65% incorrectly thought endocrinopathies due to irAEs are usually reversible, and 45% of FM residents considered antibiotics as the mainstay of treatment in ICI-mediated colitis. On a self-rated scale from 0 to 100, the median comfort level for all physicians in recognizing irAEs was 15 and for treatment of irAEs was 10. Conclusions: Significant knowledge gaps exist among residents and faculty physicians across multiple specialties regarding the recognition and treatment of irAEs due to ICIs. Given that these physicians are usually the first point of contact with patients, physician education on identification and treatment of irAEs is needed. Early detection of these toxicities is critical for their resolution.

Submitted June 1, 2022; final revision received August 8, 2022; accepted for publication August 8, 2022.

Author contributions: Conceptualization: Khalid. Formal analysis: Calderon. Investigation: Khalid. Methodology: Khalid. Software: Calderon. Supervision: Jalal, Durm. Writing—original draft: Khalid. Writing—review and editing: Calderon, Jalal, Durm.

Disclosures: Dr. Jalal has disclosed receiving grant/research support from AstraZeneca and Tesaro, and serving as a consultant for Adapt Immune. Dr. Durm has disclosed receiving grant/research support from Merck & Co., AstraZeneca, and Bristol Myers Squibb Company; and receiving honoraria from AstraZeneca and Curio Science. The remaining authors have disclosed that they have not received any financial considerations from any person or organization to support the preparation, analysis, results, or discussion of this article.

Correspondence: Ahmed Bilal Khalid, MBBS, Department of Internal Medicine, Indiana University School of Medicine, 1120 West Michigan Street, Gatch Hall 630, Indianapolis, IN 46202. Email: ahkhalid@iu.edu
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