irAE Workup Guidelines

Managing immune-related adverse events among patients who have received immune checkpoint inhibitors (ICI) can present many challenges for the multidisciplinary care team. Not only can irAEs be difficult to distinguish from other conditions, but knowing how and when to admit a patient, treat symptoms, or withhold ICI therapy can be difficult to navigate. However, in recent years, many organizations have published formal recommendations, or workup guidelines, for managing irAEs, including ASCO, ESMO, NCCN, and SITC.

The following can be used as a directory for the current irAE workup guidelines. Click to expand the organ system of interest to display the common irAEs for which guidelines are available, with details of where to find the condition-specific information in each set of guidelines.

ASCO GUIDELINES (AS OF 2018):
Brahmer JR, Lacchetti C, Schneider BJ, Atkins MB, Brassil KJ, et al. Management of immune-related adverse events in patients treated with immune checkpoint inhibitor therapy: American Society of Clinical Oncology Clinical Practice Guideline. J Clin Oncol. 2018;36(17):1714-1768 doi.org/10.1200/JCO.2017.77.6385

ESMO GUIDELINES (AS OF 2017):
Haanen JBAG, Carbonnel F, Robert C, Kerr KM, Peters S, et al. Management of toxicities from immunotherapy: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2017;28(S4): i119-i142. doi.org/10.1093/annonc/mdx225

ESMO GUIDELINES CORRECTION (AS OF 2018):
Haanen JBAG, Carbonnel F, Robert C, Kerr KM, Peters S, et al. Management of toxicities from immunotherapy: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2018;29(S4): iv264-iv266. doi.org/10.1093/annonc/mdy162

NCCN GUIDELINES (AS OF 2019):
Available on the NCCN website under NCCN Guidelines for Supportive Care, listed as Management of Immunotherapy-Related Toxicities. Login required; registration is free. https://www.nccn.org/

SITC GUIDELINES (AS OF 2017):
Puzanov I, Diab A, Abdallah K, Bingham CO 3rd, Brogdon C, et al. Managing toxicities associated with immune checkpoint inhibitors: consensus recommendations from the Society for Immunotherapy of Cancer (SITC) Toxicity Management Working Group. J ImmunoTher Cancer. 2017;5(95). DOI 10.1186/s40425-017-0300-z

Cardiovascular

Myocarditis, Pericarditis, Arrhythmias, Impaired Ventricular Function with Heart Failure and Vasculitis

• ASCO Guidelines, see page 1756, Table 9

• ESMO Guidelines, see page iv133

• NCCN Guidelines, see pages 279-282

• SITC Guidelines, see pages 12-13 (Table 3), 22-23

Venous Thromboembolism

• ASCO Guidelines, see pages 1756, 1758-1759, Table 9

Dermatologic

Bulbous Dermatoses

• ASCO Guidelines, see pages 1721-1722, Table 1

• NCCN Guidelines, see pages 260, 271-272

Pruritis

• NCCN Guidelines, see pages 259, 271-272

• SITC Guidelines, see pages 6, 7 (Table 3)

Rash/Dermatitis

• ASCO Guidelines, see pages 1716, 1720-1721, Table 1

• ESMO Guidelines, see pages iv122-iv123, Figure 3, Table 2

• NCCN Guidelines, see pages 258, 271-272

• SITC Guidelines, see pages 6, 7 (Table 3), 16

Severe Cutaneous Adverse Reactions (SCARS) (including SJS, TEN, Acute Generalized Exanthematous Pustulosis, and DRESS/DIHS)

• ASCO Guidelines, see pages 1722-1723, Table 1

• NCCN Guidelines, see pages 260, 271-272

Endocrine

Asymptomatic/Subclinical Hypothyroidism

• NCCN Guidelines, see pages 267, 275-277

Central Hypothyroidism

• NCCN Guidelines, see pages 269, 275-277

Hyperthyroidism

• ASCO Guidelines, see page 1734, Table 4

• SITC Guidelines, see page 10 (Table 3)

Hypophysitis

• ASCO Guidelines, see page 1734, Table 4

• ESMO Guidelines, see pages iv124-iv126, Figure 6, Table 2

• NCCN Guidelines, see pages 269, 275-277

• SITC Guidelines, see pages 9 (Table 3), 18

Primary Adrenal Insufficiency

• ASCO Guidelines, see page 1734, Table 4

• NCCN Guidelines, see pages 268, 275-277

Primary Hypothyroidism

• ASCO Guidelines, see pages 1730, 1734, Table 4

• ESMO Guidelines, see pages iv123-iv124, Figure 5, Table 2

• NCCN Guidelines, see pages 267, 275-277

• SITC Guidelines, see pages 9 (Table 3), 18-19

Thyrotoxicosis

• NCCN Guidelines, see pages 267, 275-277

• SITC Guidelines, see page 19

Gastrointestinal

Colitis/Diarrhea

• ASCO Guidelines, see pages 1723, 1726, Table 2

• ESMO Guidelines, see pages iv127-iv131, Figure 8, Table 2 (correction)

• NCCN Guidelines, see pages 261, 272-274

• SITC Guidelines, see pages 8 (Table 3), 16-17

Hematologic

Acquired Hemophilia

• ASCO Guidelines, see page 1755, Table 8

Acquired Thrombotic Thrombocytopenic Purpura (TTP)

• ASCO Guidelines, see page 1753, Table 8

Aplastic Anemia

• ASCO Guidelines, see pages 1753-1754, Table 8

Autoimmune Hemolytic Anemia

• ASCO Guidelines, see pages 1748, 1752-1753, Table 8

• SITC Guidelines, see pages 13 (Table 3), 23

Hemolytic Uremic Syndrome

• ASCO Guidelines, see page 1753, Table 8

Immune Thrombocytopenia

• ASCO Guidelines, see pages 1754-1755, Table 8

• SITC Guidelines, see pages 13 (Table 3), 23

Lymphopenia

• ASCO Guidelines, see page 1754, Table 8

Hepatic

Hepatitis

• ASCO Guidelines, see pages 1726-1728, Table 2

• ESMO Guidelines, see pages iv126-iv127, Figure 7, Table 2

• NCCN Guidelines, see pages 262-263, 274

• SITC Guidelines, see pages 8-9 (Table 3), 16-17

Musculoskeletal

Inflammatory Arthritis

• ASCO Guidelines, see pages 1736, 1739, Table 5

• ESMO Guidelines, see page iv133, Figure 13, Table 2

• NCCN Guidelines, see pages 280, 282-283

• SITC Guidelines, see pages 11-12 (Table 3), 20-22

Myositis

• ASCO Guidelines, see page 1739, Table 5

• NCCN Guidelines, see pages 281-283

Polymyalgia-like Syndrome

• ASCO Guidelines, see pages 1740-1741, Table 5

Nervous System

Aseptic Meningitis

• ASCO Guidelines, see page 1747, Table 7

• ESMO Guidelines, see page iv133, Figure 12, Table 2

• NCCN Guidelines, see pages 277, 279-280

Autonomic Neuropathy

• ASCO Guidelines, see page 1747, Table 7

Encephalitis

• ASCO Guidelines, see pages 1747-1748, Table 7

• ESMO Guidelines, see page iv133, Figure 12, Table 2

• NCCN Guidelines, see pages 277, 279-280

Encephalopathy/PRES

• SITC Guidelines, see page 14 (Table 3), 24

Guillain Barré Syndrome

• ASCO Guidelines, see page 1743, 1746, Table 7

• ESMO Guidelines, see page iv133, Figure 11, Table 2

• NCCN Guidelines, see pages 275, 279-280

Myasthenia Gravis

• ASCO Guidelines, see page 1743, Table 7

• ESMO Guidelines, see page iv133, Figure 11, Table 2

• NCCN Guidelines, see pages 274, 279-280

Peripheral Neuropathy

• ASCO Guidelines, see pages 1746-1747, Table 7

• NCCN Guidelines, see pages 276, 279-280

• SITC Guidelines, see page 14 (Table 3), 24

Transverse Myelitis

• ASCO Guidelines, see page 1748, Table 7

• ESMO Guidelines, see page iv133, Figure 12, Table 2

• NCCN Guidelines, see pages 278-280

Ocular

Blepharitis

• ASCO Guidelines, see page 1761

• SITC Guidelines, sees page 16 (Table 3), 24-25

Episcleritis

• ASCO Guidelines, see page 1759, Table 10

• NCCN Guidelines, see page 273

• SITC Guidelines, see pages 15-16 (Table 3), 24-25

Uveitis/Iritris

• ASCO Guidelines, see page 1759, Table 10

• ESMO Guidelines, see page iv133

• NCCN Guidelines, see pages 273, 278-279

• SITC Guidelines, see pages 15 (Table 3), 24-25

Pancreatic

Acute Pancreatitis

• NCCN Guidelines, see pages 264-265, 274

Diabetes

• ASCO Guidelines, see pages 1735-1736, Table 4

• ESMO Guidelines, see page iv126

• NCCN Guidelines, see pages 266, 275-277

• SITC Guidelines, sees page 10 (Table 3), 19

Pulmonary

Pneumonitis

• ASCO Guidelines, see pages 1728-1730, Table 3

• ESMO Guidelines, see pages iv131-iv133, Figure 9, Table 2

• NCCN Guidelines, see pages 270-271, 277-278

• SITC Guidelines, see pages 10-11 (Table 3), 19-20

Sarcoidosis

• SITC Guidelines, see pages 11 (Table 3), 20

Renal

Acute Renal Failure

• NCCN Guidelines, see pages 272, 278

Nephritis

• ASCO Guidelines, see page 1741, Table 6

• ESMO Guidelines, see page iv133, Figure 14, Table 2

• SITC Guidelines, see pages 13-14 (Table 3), 23-24

Symptomatic Nephritis

• ASCO Guidelines, see pages 1741-1743, Table 6

Additional Resources

Symptoms & Grading: National Cancer Institute. (2017). Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Available here.

Routine Monitoring Recommendations:

• NCCN Guidelines, see page 257

Industry Toxicity Management Recommendations:

• Ipilimumab (Yervoy, Bristol-Myers Squibb)

• Nivolumab (Opdivo, Bristol-Myers Squibb)

• Pembrolizumab (Keytruda, Merck & Co, Inc.)

• Atezolizumab (Tecentriq, Genentech)

• Avelumab (Bavencio, EMD Serono, Inc.)

• Durvalumab (Imfinzi, AstraZeneca)

• Cemiplimab-rwlc (Libtayo, Regeneron)

ACCC IO Wallet Card: Equip IO patients with a medical wallet card that includes the warning signs of common irAEs. Available here.