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Management of Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy: American Society of Clinical Oncology Clinical Practice Guideline

Julie R. BrahmerJulie R. Brahmer, Johns Hopkins Kimmel Cancer Center; Jennifer S. Mammen, Johns Hopkins University, Baltimore, MD; Christina Lacchetti, American Society of Clinical Oncology, Alexandria; Alexander Spira, Virginia Cancer Specialists and US Oncology Research, Fairfax, VA; Bryan J. Schneider, University of Michigan Health System, Ann Arbor, MI; Michael B. Atkins, Georgetown Lombardi Comprehensive Cancer Center; Cristina A. Reichner, Georgetown University; Laura D. Porter, Colon Cancer Alliance; Washington,Christina LacchettiJulie R. Brahmer, Johns Hopkins Kimmel Cancer Center; Jennifer S. Mammen, Johns Hopkins University, Baltimore, MD; Christina Lacchetti, American Society of Clinical Oncology, Alexandria; Alexander Spira, Virginia Cancer Specialists and US Oncology Research, Fairfax, VA; Bryan J. Schneider, University of Michigan Health System, Ann Arbor, MI; Michael B. Atkins, Georgetown Lombardi Comprehensive Cancer Center; Cristina A. Reichner, Georgetown University; Laura D. Porter, Colon Cancer Alliance; Washington,Bryan J. SchneiderJulie R. Brahmer, Johns Hopkins Kimmel Cancer Center; Jennifer S. Mammen, Johns Hopkins University, Baltimore, MD; Christina Lacchetti, American Society of Clinical Oncology, Alexandria; Alexander Spira, Virginia Cancer Specialists and US Oncology Research, Fairfax, VA; Bryan J. Schneider, University of Michigan Health System, Ann Arbor, MI; Michael B. Atkins, Georgetown Lombardi Comprehensive Cancer Center; Cristina A. Reichner, Georgetown University; Laura D. Porter, Colon Cancer Alliance; Washington,Michael B. AtkinsJulie R. Brahmer, Johns Hopkins Kimmel Cancer Center; Jennifer S. Mammen, Johns Hopkins University, Baltimore, MD; Christina Lacchetti, American Society of Clinical Oncology, Alexandria; Alexander Spira, Virginia Cancer Specialists and US Oncology Research, Fairfax, VA; Bryan J. Schneider, University of Michigan Health System, Ann Arbor, MI; Michael B. Atkins, Georgetown Lombardi Comprehensive Cancer Center; Cristina A. Reichner, Georgetown University; Laura D. Porter, Colon Cancer Alliance; Washington,Kelly BrassilJulie R. Brahmer, Johns Hopkins Kimmel Cancer Center; Jennifer S. Mammen, Johns Hopkins University, Baltimore, MD; Christina Lacchetti, American Society of Clinical Oncology, Alexandria; Alexander Spira, Virginia Cancer Specialists and US Oncology Research, Fairfax, VA; Bryan J. Schneider, University of Michigan Health System, Ann Arbor, MI; Michael B. Atkins, Georgetown Lombardi Comprehensive Cancer Center; Cristina A. Reichner, Georgetown University; Laura D. Porter, Colon Cancer Alliance; Washington,Jeffrey M. CaterinoJulie R. Brahmer, Johns Hopkins Kimmel Cancer Center; Jennifer S. Mammen, Johns Hopkins University, Baltimore, MD; Christina Lacchetti, American Society of Clinical Oncology, Alexandria; Alexander Spira, Virginia Cancer Specialists and US Oncology Research, Fairfax, VA; Bryan J. Schneider, University of Michigan Health System, Ann Arbor, MI; Michael B. Atkins, Georgetown Lombardi Comprehensive Cancer Center; Cristina A. Reichner, Georgetown University; Laura D. Porter, Colon Cancer Alliance; Washington,Ian ChauJulie R. Brahmer, Johns Hopkins Kimmel Cancer Center; Jennifer S. Mammen, Johns Hopkins University, Baltimore, MD; Christina Lacchetti, American Society of Clinical Oncology, Alexandria; Alexander Spira, Virginia Cancer Specialists and US Oncology Research, Fairfax, VA; Bryan J. Schneider, University of Michigan Health System, Ann Arbor, MI; Michael B. Atkins, Georgetown Lombardi Comprehensive Cancer Center; Cristina A. Reichner, Georgetown University; Laura D. Porter, Colon Cancer Alliance; Washington,Marc S. ErnstoffJulie R. Brahmer, Johns Hopkins Kimmel Cancer Center; Jennifer S. Mammen, Johns Hopkins University, Baltimore, MD; Christina Lacchetti, American Society of Clinical Oncology, Alexandria; Alexander Spira, Virginia Cancer Specialists and US Oncology Research, Fairfax, VA; Bryan J. Schneider, University of Michigan Health System, Ann Arbor, MI; Michael B. Atkins, Georgetown Lombardi Comprehensive Cancer Center; Cristina A. Reichner, Georgetown University; Laura D. Porter, Colon Cancer Alliance; Washington,Jennifer M. GardnerJulie R. Brahmer, Johns Hopkins Kimmel Cancer Center; Jennifer S. Mammen, Johns Hopkins University, Baltimore, MD; Christina Lacchetti, American Society of Clinical Oncology, Alexandria; Alexander Spira, Virginia Cancer Specialists and US Oncology Research, Fairfax, VA; Bryan J. Schneider, University of Michigan Health System, Ann Arbor, MI; Michael B. Atkins, Georgetown Lombardi Comprehensive Cancer Center; Cristina A. Reichner, Georgetown University; Laura D. Porter, Colon Cancer Alliance; Washington,Pamela GinexJulie R. Brahmer, Johns Hopkins Kimmel Cancer Center; Jennifer S. Mammen, Johns Hopkins University, Baltimore, MD; Christina Lacchetti, American Society of Clinical Oncology, Alexandria; Alexander Spira, Virginia Cancer Specialists and US Oncology Research, Fairfax, VA; Bryan J. Schneider, University of Michigan Health System, Ann Arbor, MI; Michael B. Atkins, Georgetown Lombardi Comprehensive Cancer Center; Cristina A. Reichner, Georgetown University; Laura D. Porter, Colon Cancer Alliance; Washington,Sigrun HallmeyerJulie R. Brahmer, Johns Hopkins Kimmel Cancer Center; Jennifer S. Mammen, Johns Hopkins University, Baltimore, MD; Christina Lacchetti, American Society of Clinical Oncology, Alexandria; Alexander Spira, Virginia Cancer Specialists and US Oncology Research, Fairfax, VA; Bryan J. Schneider, University of Michigan Health System, Ann Arbor, MI; Michael B. Atkins, Georgetown Lombardi Comprehensive Cancer Center; Cristina A. Reichner, Georgetown University; Laura D. Porter, Colon Cancer Alliance; Washington,Jennifer Holter ChakrabartyJulie R. Brahmer, Johns Hopkins Kimmel Cancer Center; Jennifer S. Mammen, Johns Hopkins University, Baltimore, MD; Christina Lacchetti, American Society of Clinical Oncology, Alexandria; Alexander Spira, Virginia Cancer Specialists and US Oncology Research, Fairfax, VA; Bryan J. Schneider, University of Michigan Health System, Ann Arbor, MI; Michael B. Atkins, Georgetown Lombardi Comprehensive Cancer Center; Cristina A. Reichner, Georgetown University; Laura D. Porter, Colon Cancer Alliance; Washington,Natasha B. LeighlJulie R. Brahmer, Johns Hopkins Kimmel Cancer Center; Jennifer S. Mammen, Johns Hopkins University, Baltimore, MD; Christina Lacchetti, American Society of Clinical Oncology, Alexandria; Alexander Spira, Virginia Cancer Specialists and US Oncology Research, Fairfax, VA; Bryan J. Schneider, University of Michigan Health System, Ann Arbor, MI; Michael B. Atkins, Georgetown Lombardi Comprehensive Cancer Center; Cristina A. Reichner, Georgetown University; Laura D. Porter, Colon Cancer Alliance; Washington,Jennifer S. MammenJulie R. Brahmer, Johns Hopkins Kimmel Cancer Center; Jennifer S. Mammen, Johns Hopkins University, Baltimore, MD; Christina Lacchetti, American Society of Clinical Oncology, Alexandria; Alexander Spira, Virginia Cancer Specialists and US Oncology Research, Fairfax, VA; Bryan J. Schneider, University of Michigan Health System, Ann Arbor, MI; Michael B. Atkins, Georgetown Lombardi Comprehensive Cancer Center; Cristina A. Reichner, Georgetown University; Laura D. Porter, Colon Cancer Alliance; Washington,David F. McDermottJulie R. Brahmer, Johns Hopkins Kimmel Cancer Center; Jennifer S. Mammen, Johns Hopkins University, Baltimore, MD; Christina Lacchetti, American Society of Clinical Oncology, Alexandria; Alexander Spira, Virginia Cancer Specialists and US Oncology Research, Fairfax, VA; Bryan J. Schneider, University of Michigan Health System, Ann Arbor, MI; Michael B. Atkins, Georgetown Lombardi Comprehensive Cancer Center; Cristina A. Reichner, Georgetown University; Laura D. Porter, Colon Cancer Alliance; Washington,Aung NaingJulie R. Brahmer, Johns Hopkins Kimmel Cancer Center; Jennifer S. Mammen, Johns Hopkins University, Baltimore, MD; Christina Lacchetti, American Society of Clinical Oncology, Alexandria; Alexander Spira, Virginia Cancer Specialists and US Oncology Research, Fairfax, VA; Bryan J. Schneider, University of Michigan Health System, Ann Arbor, MI; Michael B. Atkins, Georgetown Lombardi Comprehensive Cancer Center; Cristina A. Reichner, Georgetown University; Laura D. Porter, Colon Cancer Alliance; Washington,Loretta J. NastoupilJulie R. Brahmer, Johns Hopkins Kimmel Cancer Center; Jennifer S. Mammen, Johns Hopkins University, Baltimore, MD; Christina Lacchetti, American Society of Clinical Oncology, Alexandria; Alexander Spira, Virginia Cancer Specialists and US Oncology Research, Fairfax, VA; Bryan J. Schneider, University of Michigan Health System, Ann Arbor, MI; Michael B. Atkins, Georgetown Lombardi Comprehensive Cancer Center; Cristina A. Reichner, Georgetown University; Laura D. Porter, Colon Cancer Alliance; Washington,Tanyanika PhillipsJulie R. Brahmer, Johns Hopkins Kimmel Cancer Center; Jennifer S. Mammen, Johns Hopkins University, Baltimore, MD; Christina Lacchetti, American Society of Clinical Oncology, Alexandria; Alexander Spira, Virginia Cancer Specialists and US Oncology Research, Fairfax, VA; Bryan J. Schneider, University of Michigan Health System, Ann Arbor, MI; Michael B. Atkins, Georgetown Lombardi Comprehensive Cancer Center; Cristina A. Reichner, Georgetown University; Laura D. Porter, Colon Cancer Alliance; Washington,Laura PorterJulie R. Brahmer, Johns Hopkins Kimmel Cancer Center; Jennifer S. Mammen, Johns Hopkins University, Baltimore, MD; Christina Lacchetti, American Society of Clinical Oncology, Alexandria; Alexander Spira, Virginia Cancer Specialists and US Oncology Research, Fairfax, VA; Bryan J. Schneider, University of Michigan Health System, Ann Arbor, MI; Michael B. Atkins, Georgetown Lombardi Comprehensive Cancer Center; Cristina A. Reichner, Georgetown University; Laura D. Porter, Colon Cancer Alliance; Washington,Igor PuzanovJulie R. Brahmer, Johns Hopkins Kimmel Cancer Center; Jennifer S. Mammen, Johns Hopkins University, Baltimore, MD; Christina Lacchetti, American Society of Clinical Oncology, Alexandria; Alexander Spira, Virginia Cancer Specialists and US Oncology Research, Fairfax, VA; Bryan J. Schneider, University of Michigan Health System, Ann Arbor, MI; Michael B. Atkins, Georgetown Lombardi Comprehensive Cancer Center; Cristina A. Reichner, Georgetown University; Laura D. Porter, Colon Cancer Alliance; Washington,Cristina ReichnerJulie R. Brahmer, Johns Hopkins Kimmel Cancer Center; Jennifer S. Mammen, Johns Hopkins University, Baltimore, MD; Christina Lacchetti, American Society of Clinical Oncology, Alexandria; Alexander Spira, Virginia Cancer Specialists and US Oncology Research, Fairfax, VA; Bryan J. Schneider, University of Michigan Health System, Ann Arbor, MI; Michael B. Atkins, Georgetown Lombardi Comprehensive Cancer Center; Cristina A. Reichner, Georgetown University; Laura D. Porter, Colon Cancer Alliance; Washington,Bianca SantomassoJulie R. Brahmer, Johns Hopkins Kimmel Cancer Center; Jennifer S. Mammen, Johns Hopkins University, Baltimore, MD; Christina Lacchetti, American Society of Clinical Oncology, Alexandria; Alexander Spira, Virginia Cancer Specialists and US Oncology Research, Fairfax, VA; Bryan J. Schneider, University of Michigan Health System, Ann Arbor, MI; Michael B. Atkins, Georgetown Lombardi Comprehensive Cancer Center; Cristina A. Reichner, Georgetown University; Laura D. Porter, Colon Cancer Alliance; Washington,Carole SeigelJulie R. Brahmer, Johns Hopkins Kimmel Cancer Center; Jennifer S. Mammen, Johns Hopkins University, Baltimore, MD; Christina Lacchetti, American Society of Clinical Oncology, Alexandria; Alexander Spira, Virginia Cancer Specialists and US Oncology Research, Fairfax, VA; Bryan J. Schneider, University of Michigan Health System, Ann Arbor, MI; Michael B. Atkins, Georgetown Lombardi Comprehensive Cancer Center; Cristina A. Reichner, Georgetown University; Laura D. Porter, Colon Cancer Alliance; Washington,Alexander I. SpiraJulie R. Brahmer, Johns Hopkins Kimmel Cancer Center; Jennifer S. Mammen, Johns Hopkins University, Baltimore, MD; Christina Lacchetti, American Society of Clinical Oncology, Alexandria; Alexander Spira, Virginia Cancer Specialists and US Oncology Research, Fairfax, VA; Bryan J. Schneider, University of Michigan Health System, Ann Arbor, MI; Michael B. Atkins, Georgetown Lombardi Comprehensive Cancer Center; Cristina A. Reichner, Georgetown University; Laura D. Porter, Colon Cancer Alliance; Washington,María E. Suarez‐AlmazorJulie R. Brahmer, Johns Hopkins Kimmel Cancer Center; Jennifer S. Mammen, Johns Hopkins University, Baltimore, MD; Christina Lacchetti, American Society of Clinical Oncology, Alexandria; Alexander Spira, Virginia Cancer Specialists and US Oncology Research, Fairfax, VA; Bryan J. Schneider, University of Michigan Health System, Ann Arbor, MI; Michael B. Atkins, Georgetown Lombardi Comprehensive Cancer Center; Cristina A. Reichner, Georgetown University; Laura D. Porter, Colon Cancer Alliance; Washington,Yinghong WangJulie R. Brahmer, Johns Hopkins Kimmel Cancer Center; Jennifer S. Mammen, Johns Hopkins University, Baltimore, MD; Christina Lacchetti, American Society of Clinical Oncology, Alexandria; Alexander Spira, Virginia Cancer Specialists and US Oncology Research, Fairfax, VA; Bryan J. Schneider, University of Michigan Health System, Ann Arbor, MI; Michael B. Atkins, Georgetown Lombardi Comprehensive Cancer Center; Cristina A. Reichner, Georgetown University; Laura D. Porter, Colon Cancer Alliance; Washington,Jeffrey S. WeberJulie R. Brahmer, Johns Hopkins Kimmel Cancer Center; Jennifer S. Mammen, Johns Hopkins University, Baltimore, MD; Christina Lacchetti, American Society of Clinical Oncology, Alexandria; Alexander Spira, Virginia Cancer Specialists and US Oncology Research, Fairfax, VA; Bryan J. Schneider, University of Michigan Health System, Ann Arbor, MI; Michael B. Atkins, Georgetown Lombardi Comprehensive Cancer Center; Cristina A. Reichner, Georgetown University; Laura D. Porter, Colon Cancer Alliance; Washington,Jedd D. WolchokJulie R. Brahmer, Johns Hopkins Kimmel Cancer Center; Jennifer S. Mammen, Johns Hopkins University, Baltimore, MD; Christina Lacchetti, American Society of Clinical Oncology, Alexandria; Alexander Spira, Virginia Cancer Specialists and US Oncology Research, Fairfax, VA; Bryan J. Schneider, University of Michigan Health System, Ann Arbor, MI; Michael B. Atkins, Georgetown Lombardi Comprehensive Cancer Center; Cristina A. Reichner, Georgetown University; Laura D. Porter, Colon Cancer Alliance; Washington,John A. ThompsonJulie R. Brahmer, Johns Hopkins Kimmel Cancer Center; Jennifer S. Mammen, Johns Hopkins University, Baltimore, MD; Christina Lacchetti, American Society of Clinical Oncology, Alexandria; Alexander Spira, Virginia Cancer Specialists and US Oncology Research, Fairfax, VA; Bryan J. Schneider, University of Michigan Health System, Ann Arbor, MI; Michael B. Atkins, Georgetown Lombardi Comprehensive Cancer Center; Cristina A. Reichner, Georgetown University; Laura D. Porter, Colon Cancer Alliance; Washington,
2018en
ABI

Abstract

Purpose To increase awareness, outline strategies, and offer guidance on the recommended management of immune-related adverse events in patients treated with immune checkpoint inhibitor (ICPi) therapy. Methods A multidisciplinary, multi-organizational panel of experts in medical oncology, dermatology, gastroenterology, rheumatology, pulmonology, endocrinology, urology, neurology, hematology, emergency medicine, nursing, trialist, and advocacy was convened to develop the clinical practice guideline. Guideline development involved a systematic review of the literature and an informal consensus process. The systematic review focused on guidelines, systematic reviews and meta-analyses, randomized controlled trials, and case series published from 2000 through 2017. Results The systematic review identified 204 eligible publications. Much of the evidence consisted of systematic reviews of observational data, consensus guidelines, case series, and case reports. Due to the paucity of high-quality evidence on management of immune-related adverse events, recommendations are based on expert consensus. Recommendations Recommendations for specific organ system-based toxicity diagnosis and management are presented. While management varies according to organ system affected, in general, ICPi therapy should be continued with close monitoring for grade 1 toxicities, with the exception of some neurologic, hematologic, and cardiac toxicities. ICPi therapy may be suspended for most grade 2 toxicities, with consideration of resuming when symptoms revert to grade 1 or less. Corticosteroids may be administered. Grade 3 toxicities generally warrant suspension of ICPis and the initiation of high-dose corticosteroids (prednisone 1 to 2 mg/kg/d or methylprednisolone 1 to 2 mg/kg/d). Corticosteroids should be tapered over the course of at least 4 to 6 weeks. Some refractory cases may require infliximab or other immunosuppressive therapy. In general, permanent discontinuation of ICPis is recommended with grade 4 toxicities, with the exception of endocrinopathies that have been controlled by hormone replacement. Additional information is available at www.asco.org/supportive-care-guidelines and www.asco.org/guidelineswiki .

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