Overview and management of toxicities of immune checkpoint-blocking drugs
and | Sep 17, 2016
About this article
Article Category: Research Article
Published Online: Sep 17, 2016
Page range: 28 - 37
Received: May 27, 2016
Accepted: May 30, 2016
DOI: https://doi.org/10.1515/fco-2016-0004
Keywords
© 2016
This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.
Management of immune-related adverse events.
| Grade | Grade 1 | Grade 2 | Grade 3 | Grade 4 |
|---|---|---|---|---|
| No ICI interruption Hydration Specific diet, loperamide | Withhold ICI. As grade 1 if patient well. If no improvement in 5 days/ worsening of symptoms start prednisone 0.5–1 mg/kg (tapering over 2–4 weeks). If no improvement with steroids, manage as per grade 3. Consider colonoscopy. | Permanently discontinue ICI. Hospitalisation required. Start prednisone 1–2 mg/kg. If no improvement in 2–3 days, start infliximab 5 mg/kg (if no sepsis/ perforation) with synchronous administration of steroids. Once resolved to grade 1, taper steroids over minimum one month. In infliximab-refractory cases, mycophenylate mofetil can be used. Colonoscopy recommended. | Permanently discontinue ICI. As per grade 3. Gastrenterologist and surgeon consultation recommended. | |
| No ICI interruption. Topical corticosteroid ointments | Withhold ICI. Initially manage with topical corticosteroid ointments. If no improvement in one week, start IV prednisone 0.5 mg/kg. Restart treatment once toxicity resolves to grade 1. | Permanently discontinue ICI. Start prednisone 1–2 mg/kg. Skin biopsy and dermatological consultation recommended. Hospitalisation might be required. | Permanently discontinue ICI. Manage as per grade 3. Hospitalisation required. | |
| No ICI interruption. Check for other causes. | Withhold ICI. Start prednisone 1–2 mg/kg. Continue until toxicity resolves to grade 1. Tapering over 1 month. | Permanently discontinue ICI. Start prednisone 1–2 mg/kg. Continue until toxicity resolves to grade 1. In rare cases of corticosteroid refractory hepatitis, mecophenolate mofetil (500 mg every 12 hours) should be given. Consider liver biopsy. Hospitalisation if liver enzyme levels >8 UPN | Permanently discontinue ICI. As per grade 3. | |
| No ICI interruption. Endocrinology consultation for hormone replacement. | Withhold ICI. Start prednisone 1mg/kg. Endocrinology consultation for hormone replacement. | Permanently discontinue ICI. Start prednisone 1–2 mg/kg. Endocrinology consultation for hormone replacement. | Permanently discontinue ICI. As per grade 3. | |
| No ICI interruption. Monitor. | No ICI interruption. Start levothyroxine. | Start prednisone 1–2 mg/kg. Hospitalisation and endocrinology consultation recommended. | As per grade 3. | |
| No ICI interruption. Monitor. | Endocrinology consultation. Propranolol for symptoms. Steroids or carbimazole might be needed. | Start prednisone 1–2 mg/kg. Hospitalisation and endocrinology consultation recommended. | As per grade 3. | |
| Delay drug administration. Exclude other causes. Monitoring and management reassessment. | Withhold ICI. Start prednisone 1–2 mg/kg. Consider hospitalisation. Consider empiric antibiotics. Taper steroids if improvement noticed. If no improvement, treat as grade 3. | Permanently discontinue ICI. Hospitalisation required. Exclude other causes (bronchoscopy). Add antibiotics for opportunistic infections. If no improvement, add infliximab. If improvement, taper steroids. | Permanently discontinue ICI. As per grade 3. Consider admission to ITU. | |
| No ICI interruption. Exclude other causes. Monitoring. | Withhold ICI. Exclude other causes. Start prednisone 0.5–1 mg/kg. If no improvement, manage as per grade 3. | Permanently discontinue ICI. Start prednisone 1–2 mg/kg. Consider renal biopsy. | As per grade 3. |