TY - JOUR T1 - Managing toxicities associated with immune checkpoint inhibitors: consensus recommendations from the Society for Immunotherapy of Cancer (SITC) Toxicity Management Working Group JF - Journal for ImmunoTherapy of Cancer JO - J Immunother Cancer DO - 10.1186/s40425-017-0300-z VL - 5 IS - 1 SP - 95 AU - I. Puzanov AU - A. Diab AU - K. Abdallah AU - C. O. Bingham III AU - C. Brogdon AU - R. Dadu AU - L. Hamad AU - S. Kim AU - M. E. Lacouture AU - N. R. LeBoeuf AU - D. Lenihan AU - C. Onofrei AU - V. Shannon AU - R. Sharma AU - A. W. Silk AU - D. Skondra AU - M. E. Suarez-Almazor AU - Y. Wang AU - K. Wiley AU - H. L. Kaufman AU - M. S. Ernstoff AU - on behalf of the Society for Immunotherapy of Cancer Toxicity Management Working Group AU - Jeff Anderson AU - Deborah Arrindell AU - Stephanie Andrews AU - Joan Ballesteros AU - Janie Boyer AU - Daniel Chen AU - David Chonzi AU - Ion Cotarla AU - Renato Cunha AU - Marianne Davies AU - Michelle Dawson AU - Adam Dicker AU - Lisa Eifler AU - Andrew Ferguson AU - Cristiano Ferlini AU - Stanley Frankel AU - William Go AU - Celestine Gochett AU - Jenna Goldberg AU - Priscila Goncalves AU - Trishna Goswami AU - Nancy Gregory AU - James L. Gulley AU - Vinny Hayreh AU - Nicole Helie AU - William Holmes AU - Jer-Yuan Hsu AU - Ramy Ibrahim AU - Cecilia Larocca AU - Kimberly Lehman AU - Sergio Ley-Acosta AU - Olivier Lambotte AU - Jason Luke AU - Joan McClure AU - Elisabete Michelon AU - Mary Nakamura AU - Kiran Patel AU - Bilal Piperdi AU - Zeshaan Rasheed AU - Dan Reshef AU - Joanne Riemer AU - Caroline Robert AU - Makan Sarkeshik AU - Ann Saylors AU - Judy Schreiber AU - Kim Shafer-Weaver AU - William Sharfman AU - Elad Sharon AU - Richard Sherry AU - Cyndy Simonson AU - Cherry Thomas AU - John A. Thompson AU - Elizabeth Trehu AU - Dina Tresnan AU - Michelle Turner AU - Darshan Wariabharaj AU - Ian Waxman AU - Lauren Wood AU - Lin Zhang AU - Pan Zheng Y1 - 2017/12/01 UR - http://jitc.bmj.com/content/5/1/95.abstract N2 - Cancer immunotherapy has transformed the treatment of cancer. However, increasing use of immune-based therapies, including the widely used class of agents known as immune checkpoint inhibitors, has exposed a discrete group of immune-related adverse events (irAEs). Many of these are driven by the same immunologic mechanisms responsible for the drugs’ therapeutic effects, namely blockade of inhibitory mechanisms that suppress the immune system and protect body tissues from an unconstrained acute or chronic immune response. Skin, gut, endocrine, lung and musculoskeletal irAEs are relatively common, whereas cardiovascular, hematologic, renal, neurologic and ophthalmologic irAEs occur much less frequently. The majority of irAEs are mild to moderate in severity; however, serious and occasionally life-threatening irAEs are reported in the literature, and treatment-related deaths occur in up to 2% of patients, varying by ICI. Immunotherapy-related irAEs typically have a delayed onset and prolonged duration compared to adverse events from chemotherapy, and effective management depends on early recognition and prompt intervention with immune suppression and/or immunomodulatory strategies. There is an urgent need for multidisciplinary guidance reflecting broad-based perspectives on how to recognize, report and manage organ-specific toxicities until evidence-based data are available to inform clinical decision-making. The Society for Immunotherapy of Cancer (SITC) established a multidisciplinary Toxicity Management Working Group, which met for a full-day workshop to develop recommendations to standardize management of irAEs. Here we present their consensus recommendations on managing toxicities associated with immune checkpoint inhibitor therapy.Abbreviations:2-D echoTwo-dimensional echocardiogram/echocardiography6MWT6 min walk testAACRAmerican Association for Cancer ResearchACCCAssociation of Community Cancer CentersACPAAnti-citrullinated protein antibodiesACTHAdrenocorticotropic hormoneADCCAntibody-dependent cell-mediated cytotoxicityADLActivities of daily livingALTAlanine aminotransferaseANAAntinuclear antibodyAnti-CCPCyclic citrullinated peptide antibodyAnti-RFAnti-rheumatoid factor (anti-RF)Anti-TNFAnti-tumor necrosis factorASCOAmerican Society of Clinical OncologyASTAspartate aminotransferaseATGAnti-thymocyte globulinBALBronchoalveolar lavageBIDTwo times dailyBNPB-type natriuretic peptideBSABody surface areaCBCComplete blood countCKCreatine kinaseCMPComplete metabolic panelCMVCytomegalovirusCNSCentral Nervous SystemCOPCryptogenic organizing pneumoniaCOPDChronic obstructive pulmonary diseaseCRPC-reactive proteinCTComputed tomographyCTCAECommon Terminology Criteria for Adverse EventsCTLA-4Cytotoxic T lymphocyte-antigen-4DICDisseminated intravascular coagulationDLCODiffusing capacity of the lungs for carbon monoxideDMARDSDisease modifying anti-rheumatic drugsDRESSDrug rash with eosinophilia and systemic symptomsEBUSEndobronchial ultrasoundECGElectrocardiogramESRErythrocyte sedimentation rateFDAU.S. Food and Drug AdministrationFDG-PETFluorodeoxyglucose positron emission tomographyFNAFine needle aspirationFOBTFecal occult blood testFreeT4Free thyroxineFSHFollicle-stimulating hormoneFVCForced vital capacityGAD65Glutamic acid decarboxylaseGCAGiant cell arteritisGIGastrointestinalHbA1cGlycated hemoglobinHBcAbHepatitis B core antibodyHBsAbHepatitis B surface antibodyHBsAgHepatitis B surface antigenHCAbHepatitis C antibodyHgbHemoglobinHIVHuman immunodeficiency virusHPHypersensitivity pneumonitisHRTHormone Replacement TherapyHSVHerpes simplex virusIBDInflammatory bowel diseaseICIsImmune checkpoint inhibitorsICUIntensive care unitIFImmunofluorescenceIgEImmunoglobulin EIgG1Immunoglobulin G1IgG4Immunoglobulin G4irAEsImmune-related adverse eventsIVIGIntravenous immunoglobulinLHLuteinizing hormoneLLNLower limit of NormalmAbsMonoclonal antibodiesMCPMetacarpophalangealMedDRAMedical Dictionary for Regulatory ActivitiesMRIMagnetic resonance imagingNCCNNational Comprehensive Cancer NetworkNCINational Cancer InstituteNIHNational Institutes of HealthNSCLCNon-small cell lung carcinomaNSIPNonspecific interstitial pneumonitisNT pro-BNPN-terminal pro B-type natriuretic peptideONSOncology Nursing SocietyPASIpsoriasis area severity indexPCRPolymerase chain reactionPD-1Programmed cell death protein-1PD-L1Programmed cell death-ligand 1PFPulmonary fibrosisPFTsPulmonary function testsPIPProximal interphalangealPMRPolymyalgia rheumaticPRESPosterior Reversible Encephalopathy SyndromeQIDFour times dailyRARheumatoid arthritisRAIUSRadioactive iodine uptake scanSITCSociety for Immunotherapy of CancerSJS/TENStevens-Johnson Syndrome/toxic epidermal necrolysisSLESystemic lupus erythematosusT1DMType I DiabetesT3TriiodothyronineTBBxTransbronchial lung biopsyTcTechnetiumTh17.1T helper 17 cellsTLCTotal lung capacityTNFiTumor necrosis factor inhibitorTPOThyroid peroxidaseTRAbThyroid-stimulating hormone receptor antibodyTSHThyroid-stimulating hormoneTSIThyroid-stimulating immunoglobulinUIPUsual interstitial pneumonitisULNUpper Limit of NormalUVBShort wave ultraviolet BVZVVaricella zoster virusZn-T8Zinc transporter 8 ER -