Table 2.
General approach for management of immune-related adverse events
| irAE | ICI therapy | Immunosuppressants | Other treatment |
|---|---|---|---|
| Grade 1 | Discontinue if hypophysitis, pneumonitis, and/or sarcoidosis Consider holding if renal Hold if neurologic, aplastic anemia, acquired hemophilia Continue for all others | Prednisone 0.5-1 mg/kg/day if acquired hemophilia | Topical steroidsa, oral antihistaminesb, topical emollients if dermatologic |
| Loperamide if gastrointestinalc | |||
| Thyroid hormone supplementationd if hypothyroidism | |||
| Beta-blockers for symptomatic hyperthyroidisme; insulin therapy if hyperglycemia | |||
| Oral fluids, loperamide, hormone replacement therapyf if hypophysitis | |||
| Consider artificial tears if ocular | |||
| Analgesicsg if rheumatologic | |||
| Grade 2 | Considering holding if dermatologic, rheumatologic, or lymphopenia Hold for all others | Prednisone 0.5-1 mg/kg/dayh
Prednisone 1-2 mg/kg/day if hypophysitisi Prednisone 2 mg/kg/day if transverse myelitisk |
In addition to the above, consider: Adding infliximab if gastrointestinalj |
| Empiric antibiotics if pulmonary | |||
| Prednisone 2 mg/kg/day if transverse myelitisk | |||
| Adding ATG and cyclosporine if aplastic anemia | |||
| Adding GABA agonistl or duloxetine for pain if peripheral neuropathy Adding ophthalmic prednisone if ocular | |||
| Grade 3 | Discontinue if hepatitis, renal, ocular, neurologic, cardiovascular, rheumatologic, and/or hematologic Hold for all others | Prednisone 1-2 mg/kg/day Prednisone 2-4 mg/kg/day if peripheral neuropathy or Guillain-Barre syndrome Consider plasmapheresis, intravenous immunoglobulin therapy, methotrexate, azathioprine, or mycophenolate mofetil through Grade 4 if myositis; Consider methotrexate or tocilizumab through Grade 4 if Consider rituximab or cyclophosphamide if acquired hemophilia |
In addition to the above, consider: Adding omalizumab, GABA agonistl if pruritis Plasmapheresis or immunoglobulin if neurologic Pyridostigminem if myasthenia gravis Antirheumatic drugsn, methotrexate, infliximab or tocilizumab if refractory arthritis or polymyalgia-like syndrome Infliximab, mycophenolate mofetil, intravenous immunoglobulin if pulmonary or renal Rituximab if autoimmune encephalopathy infliximab if cardiovascularo |
| Grade 4 | Discontinue | Prednisone 2-4 mg/kg/day | In addition to the above, consider: Adding mycophenolate mofetil if hepatitisp empiric antiviralsq if aseptic meningitis and/or encephalitis rituximab if acquired TTPr
rituximab or cyclophosphamide if acquired hemophilia rituximab, intravenous immunoglobulin, cyclosporine A, or mycophenolate mofetil if autoimmune hemolytic anemia eculizaumabs if hemolytic uremic syndrome intravenous immunoglobulin, rituximab, or thrombopoietin receptor agonists if immune thrombocytopenia |
aClobetasol dipronate 0.05% or equivalent; bCetirizine, hydroxyzine, or equivalent; cAvoid for Clostridium difficile; dLevothyroxine 1.6 mcg/kg or 25-50 mcg in elderly; eAtenolol 25-50 mg; fThyroid, testosterone, estrogen; gAcetaminophen or nonsteroidal anti-inflammatory drugs; hConsider starting at 1 mg/kg/day if gastrointestinal; iConsider infliximab, MMF, tacrolimus, or loperamide through Grade 4; jInfliximab-refractory is noted if no response is seen in 2 days; kIntravenous immunoglobulin or plasmapheresis is strongly recommended; lGabapentin, pregabalin, or equaivalent if neuropathic-related; mPyridostigmine 30 mg three times a day; nSulfasalazine, methotrexate, leflunamide; oHigh-dose prednisone for myocarditis; pAvoid infliximab for hepatitis; qIntravenous acyclovir; rPrednisone 1 g intravenously for TTP; sEculizumab 900 mg weekly for four doses, 1200 mg week 5, then 1200 mg every 2 weeks. ATG: Antithymocyte globulin, GABA: Gamma-aminobutyric acid, TTP: Thrombotic thrombocytopenic purpura, ICI: Immune checkpoint inhibitor, MMF: Mycophenolate mofetil