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Managing toxicities associated with immune checkpoint inhibitors: consensus recommendations from the Society for Immunotherapy of Cancer (SITC) Toxicity Management Working Group

Abstract

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.

  • Immune-related adverse events
  • Toxicity
  • Immune checkpoint inhibitor
  • Abbreviations:
    2-D echo
    Two-dimensional echocardiogram/echocardiography
    6MWT
    6 min walk test
    AACR
    American Association for Cancer Research
    ACCC
    Association of Community Cancer Centers
    ACPA
    Anti-citrullinated protein antibodies
    ACTH
    Adrenocorticotropic hormone
    ADCC
    Antibody-dependent cell-mediated cytotoxicity
    ADL
    Activities of daily living
    ALT
    Alanine aminotransferase
    ANA
    Antinuclear antibody
    Anti-CCP
    Cyclic citrullinated peptide antibody
    Anti-RF
    Anti-rheumatoid factor (anti-RF)
    Anti-TNF
    Anti-tumor necrosis factor
    ASCO
    American Society of Clinical Oncology
    AST
    Aspartate aminotransferase
    ATG
    Anti-thymocyte globulin
    BAL
    Bronchoalveolar lavage
    BID
    Two times daily
    BNP
    B-type natriuretic peptide
    BSA
    Body surface area
    CBC
    Complete blood count
    CK
    Creatine kinase
    CMP
    Complete metabolic panel
    CMV
    Cytomegalovirus
    CNS
    Central Nervous System
    COP
    Cryptogenic organizing pneumonia
    COPD
    Chronic obstructive pulmonary disease
    CRP
    C-reactive protein
    CT
    Computed tomography
    CTCAE
    Common Terminology Criteria for Adverse Events
    CTLA-4
    Cytotoxic T lymphocyte-antigen-4
    DIC
    Disseminated intravascular coagulation
    DLCO
    Diffusing capacity of the lungs for carbon monoxide
    DMARDS
    Disease modifying anti-rheumatic drugs
    DRESS
    Drug rash with eosinophilia and systemic symptoms
    EBUS
    Endobronchial ultrasound
    ECG
    Electrocardiogram
    ESR
    Erythrocyte sedimentation rate
    FDA
    U.S. Food and Drug Administration
    FDG-PET
    Fluorodeoxyglucose positron emission tomography
    FNA
    Fine needle aspiration
    FOBT
    Fecal occult blood test
    FreeT4
    Free thyroxine
    FSH
    Follicle-stimulating hormone
    FVC
    Forced vital capacity
    GAD65
    Glutamic acid decarboxylase
    GCA
    Giant cell arteritis
    GI
    Gastrointestinal
    HbA1c
    Glycated hemoglobin
    HBcAb
    Hepatitis B core antibody
    HBsAb
    Hepatitis B surface antibody
    HBsAg
    Hepatitis B surface antigen
    HCAb
    Hepatitis C antibody
    Hgb
    Hemoglobin
    HIV
    Human immunodeficiency virus
    HP
    Hypersensitivity pneumonitis
    HRT
    Hormone Replacement Therapy
    HSV
    Herpes simplex virus
    IBD
    Inflammatory bowel disease
    ICIs
    Immune checkpoint inhibitors
    ICU
    Intensive care unit
    IF
    Immunofluorescence
    IgE
    Immunoglobulin E
    IgG1
    Immunoglobulin G1
    IgG4
    Immunoglobulin G4
    irAEs
    Immune-related adverse events
    IVIG
    Intravenous immunoglobulin
    LH
    Luteinizing hormone
    LLN
    Lower limit of Normal
    mAbs
    Monoclonal antibodies
    MCP
    Metacarpophalangeal
    MedDRA
    Medical Dictionary for Regulatory Activities
    MRI
    Magnetic resonance imaging
    NCCN
    National Comprehensive Cancer Network
    NCI
    National Cancer Institute
    NIH
    National Institutes of Health
    NSCLC
    Non-small cell lung carcinoma
    NSIP
    Nonspecific interstitial pneumonitis
    NT pro-BNP
    N-terminal pro B-type natriuretic peptide
    ONS
    Oncology Nursing Society
    PASI
    psoriasis area severity index
    PCR
    Polymerase chain reaction
    PD-1
    Programmed cell death protein-1
    PD-L1
    Programmed cell death-ligand 1
    PF
    Pulmonary fibrosis
    PFTs
    Pulmonary function tests
    PIP
    Proximal interphalangeal
    PMR
    Polymyalgia rheumatic
    PRES
    Posterior Reversible Encephalopathy Syndrome
    QID
    Four times daily
    RA
    Rheumatoid arthritis
    RAIUS
    Radioactive iodine uptake scan
    SITC
    Society for Immunotherapy of Cancer
    SJS/TEN
    Stevens-Johnson Syndrome/toxic epidermal necrolysis
    SLE
    Systemic lupus erythematosus
    T1DM
    Type I Diabetes
    T3
    Triiodothyronine
    TBBx
    Transbronchial lung biopsy
    Tc
    Technetium
    Th17.1
    T helper 17 cells
    TLC
    Total lung capacity
    TNFi
    Tumor necrosis factor inhibitor
    TPO
    Thyroid peroxidase
    TRAb
    Thyroid-stimulating hormone receptor antibody
    TSH
    Thyroid-stimulating hormone
    TSI
    Thyroid-stimulating immunoglobulin
    UIP
    Usual interstitial pneumonitis
    ULN
    Upper Limit of Normal
    UVB
    Short wave ultraviolet B
    VZV
    Varicella zoster virus
    Zn-T8
    Zinc transporter 8
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