A Multidisciplinary Toxicity Team for Cancer Immunotherapy–Related Adverse Events

Authors:
Jarushka Naidoo Bloomberg-Kimmel Institute for Cancer Immunotherapy, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins;

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Jiajia Zhang Bloomberg-Kimmel Institute for Cancer Immunotherapy, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins;

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Evan J. Lipson Bloomberg-Kimmel Institute for Cancer Immunotherapy, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins;

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Patrick M. Forde Bloomberg-Kimmel Institute for Cancer Immunotherapy, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins;

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Karthik Suresh Department of Medicine, Division of Pulmonary and Critical Care Medicine,

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Kendall F. Moseley Department of Medicine, Division of Endocrinology, Diabetes & Metabolism,

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Seema Mehta Department of Medicine, Division of Infectious Diseases,

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Shawn G. Kwatra Department of Medicine, Division of Dermatology,

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Alyssa M. Parian Department of Medicine, Division of Gastroenterology,

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Amy K. Kim Department of Medicine, Division of Gastroenterology,

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John C. Probasco Department of Medicine, Division of Neurology,

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Rosanne Rouf Department of Medicine, Division of Cardiology,

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Jennifer E. Thorne Department of Medicine, Division of Ophthalmology,
Department of Epidemiology, and

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Satish Shanbhag Bloomberg-Kimmel Institute for Cancer Immunotherapy, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins;

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Joanne Riemer Bloomberg-Kimmel Institute for Cancer Immunotherapy, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins;

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Ami A. Shah Department of Medicine, Division of Rheumatology, Johns Hopkins University School of Medicine, Baltimore, Maryland.

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Drew M. Pardoll Bloomberg-Kimmel Institute for Cancer Immunotherapy, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins;

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Clifton O. Bingham III Department of Medicine, Division of Rheumatology, Johns Hopkins University School of Medicine, Baltimore, Maryland.

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Julie R. Brahmer Bloomberg-Kimmel Institute for Cancer Immunotherapy, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins;

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Laura C. Cappelli Department of Medicine, Division of Rheumatology, Johns Hopkins University School of Medicine, Baltimore, Maryland.

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Background: Immune checkpoint inhibitors (ICIs) may cause immune-related adverse events (irAEs). Methods to obtain real-time multidisciplinary input for irAEs that require subspecialist care are unknown. This study aimed to determine whether a virtual multidisciplinary immune-related toxicity (IR-tox) team of oncology and medicine subspecialists would be feasible to implement, be used by oncology providers, and identify patients for whom multidisciplinary input is sought. Patients and Methods: Patients treated with ICIs and referred to the IR-tox team in August 2017 through March 2018 were identified. Feasibility was defined as receipt of electronic referrals and provision of recommendations within 24 hours of referral. Use was defined as the proportion of referring providers who used the team’s recommendations, which was determined through a postpilot survey. Demographics and tumor, treatment, and referral data were collected. Patient features and irAE associations were analyzed. Results: The IR-tox team was found to be feasible and used: 117 referrals from 102 patients were received in 8 months, all providers received recommendations within 24 hours, 100% of surveyed providers used the recommendations, and 74% changed patient management based on IR-tox team recommendations. Referrals were for suspected irAEs (n=106; 91%) and suitability to treat with ICIs (n=11; 10%). In referred patients, median age was 64 years, 54% were men, 13% had prior autoimmunity, and 46% received ICI combinations versus monotherapy (54%). The most commonly referred toxicities were pneumonitis (23%), arthritis (16%), and dermatitis (15%); 15% of patients had multisystem toxicities. Multiple referrals were more common in those treated with combination ICIs (odds ratio [OR], 6.0; P=.035) or with multisystem toxicities (OR, 8.1; P=.005). The IR-tox team provided a new multidisciplinary forum to assist providers in diagnosing and managing complex irAEs. This model identifies educational and service needs, and patients with irAEs for whom multidisciplinary care is most sought. Conclusions: A virtual multidisciplinary toxicity team for irAEs was a feasible and used service, and facilitated toxicity identification and management.

Submitted October 3, 2018; accepted for publication January 4, 2019.

Author contributions: Study concept and design: Naidoo, Lipson, Forde, Shah, Pardoll, Bingham, Brahmer, Cappelli. Data acquisition: Naidoo, Zhang, Cappelli. Data analysis and interpretation: All authors. Drafting of manuscript: All authors.

Disclosures: Dr. Naidoo has disclosed that she is a consultant for AstraZeneca, Bristol-Myers Squibb, and Takeda; receives grant/research support from Merck, AstraZeneca/MedImmune, Calithera, and Kyowa Hakko Kirin; and receives honoraria from AstraZeneca/MedImmune and Bristol-Myers Squibb. Dr. Lipson has disclosed that he is a consultant for Bristol-Myers Squibb, Novartis, EMD Serono, Array BioPharma, Regeneron/Sanofi Genzyme, Macrogenics, Merck, and Millennium; and receives grant/research support from Bristol-Myers Squibb, Merck, and Sysmex. Dr. Forde has disclosed that he is a consultant for Bristol-Myers Squibb, AstraZeneca/MedImmune, Novartis, AbbVie, Boehringer, Celgene, and Eli Lilly, and receives grant/research support from Bristol-Myers Squibb, AstraZeneca/MedImmune, Novartis, and Kyowa Hakko Kirin. Dr. Thorne has disclosed that she is a consultant for Gilead, Santen, and AbbVie. Dr. Shanbhag has disclosed that he receives grant/research support from Daiichi-Sankyo, and is a scientific advisor for Takeda Oncology. Ms. Riemer has disclosed that she is a consultant for Bristol-Myers Squibb, EMD Serono, and AstraZeneca/MedImmune. Dr. Shah has disclosed that she serves as a consultant to Bristol-Myers Squibb. Dr. Pardoll has disclosed that he is a consultant for Aduro Biotech, Amgen, AstraZeneca/MedImmune/Amplimmune, Bayer, Camden Nexus II, Compugen, DNATRIX, Dynavax Technologies Corporation, Five Prime Therapeutics, Rock Springs Capital, Tizona, Janssen, Immunomic Therapeutics, Merck, WindMIL, FLX Bio, and Ervaxx; receives grant/research support from Bristol-Myers Squibb; and has an IP License from Bristol-Myers Squibb, Compugen, and Potenza. Dr. Bingham has disclosed that he is a consultant for and receives grant/research support from Bristol-Myers Squibb. Dr. Brahmer has disclosed that she is a consultant for Bristol-Myers Squibb, AstraZeneca/MedImmune, Genentech, Celgene, Eli Lilly, Merck, Amgen, and Syntax, and receives grant/research support from Bristol-Myers Squibb, AstraZeneca/MedImmune, Incyte, and Merck. Dr. Cappelli has disclosed that she receives grant/research support from Bristol-Myers Squibb. The remaining authors have not received any financial consideration from any person or organization to support the preparation, analysis, results, or discussion of this article.

Correspondence: Jarushka Naidoo, MBBCh, Johns Hopkins Bayview, 301 Mason Lord Drive, Baltimore, MD 21224. Email: jnaidoo1@jhmi.edu

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