Introduction to Diagnosing and Managing Immune-mediated Adverse Events (imAEs)

Immuno-oncology (IO) treatments are now considered standard therapy options for many types of cancer. However, along with checkpoint inhibition, comes a unique set of possible side effects termed imAEs.1,2

“As immuno-oncology treatments multiply, one challenge for physicians is learning to recognize and manage unique immune-mediated adverse events.” —Dr Antonia

imAEs: Introduction

Watch Scott Antonia, MD, PhD, medical oncologist and Chair of the Thoracic Oncology Department at the Moffitt Cancer Center in Tampa, Florida give a brief introduction to imAEs in immuno-oncology.

Video Chapters

Monitoring imAEs

Since imAEs can be different from what is expected with chemotherapy, it’s important to understand the safety profile of the specific treatment and encourage your patients to track any symptoms they may experience.2,6

The organs most commonly affected by imAEs are skin, liver (hepatitis), kidneys (nephritis), gastrointestinal tract (diarrhea and colitis), lungs (pneumonitis), and endocrine organs (hyperthyroidism, hypothyroidism, and hypophysitis). However, imAEs can affect any organ or tissue.2,6,7

If left untreated, imAEs could progress to become harmful or life-threatening conditions.5,6

Diagnosing imAEs

Educate your patients. Make sure they1,6:

  • Understand imAE symptoms to look for
  • Immediately report unusual signs and symptoms
  • Go directly to the oncologist’s office for symptom evaluation and/or treatment

Monitor your patients’ health4-6:

  • Schedule blood testing (CBC, renal, hepatic, pancreatic, thyroid)
  • Schedule patients for regular visits for blood and symptom monitoring
  • Encourage patients to track their symptoms

Although regular diagnostic workups include routine laboratory tests, in cases of pneumonitis or hypophysitis, imaging (high-resolution CT, MRI, or radiography) can confirm diagnosis.1,5

Managing imAEs

Early recognition and monitoring of all imAEs can help manage adverse events before they become more serious and cause treatment interruption.5,6

Create an action plan2,6

  • Follow a clear management algorithm for all grades of toxicities
  • Understand when a specialist should be contacted to help manage imAEs

Intervene when necessary5

  • Take immediate action, even for Grade 1 toxicities
  • Hold dosing until symptoms resolve
  • Start with OTC medications, initiate steroids early if needed

In general, the management of imAEs may include the use of corticosteroids or other immunosuppressive agents. Consult applicable product label for specific recommendations.3,5

Common imAEs

Watch the videos below to learn more about the diagnosis and treatment of imAEs related to the most commonly affected organs.

“Patients should be counseled, educated on those sorts of symptoms to look out for and report, because those symptoms may occur before we as treating physicians are aware of it based on blood abnormalities.” —Dr Antonia

imAEs: Endocrine System

Watch Scott Antonia, MD, PhD, medical oncologist and Chair of the Thoracic Oncology Department at the Moffitt Cancer Center in Tampa, Florida, discuss the diagnosis and treatment of hyperthyroidism, hypothyroidism, hypophysitis, and related imAEs.

Video Chapters

“The activation of the immune system can generate a number of so-called immune-related adverse events. And I would say the most common one is colitis.” —Dr Maio

imAEs: Gastrointestinal Tract

Watch Michele Maio, MD, PhD, Director of the division of Medical Oncology and Immunotherapy at the University Hospital of Siena, Italy, discuss the diagnosis and treatment of diarrhea, colitis, and related imAEs.

Video Chapters

“Immune-related nephritis is, luckily, a fairly rare scenario. It occurs well under 1% of the time.” —Dr Weber

imAEs: Kidneys

Watch Jeffrey Weber, MD, PhD, medical oncologist and Deputy Director at the Perlmutter Cancer Center at the NYU Langone Medical Center in New York, discuss the diagnosis and treatment of nephritis and related imAEs.

Video Chapters

“Hepatitis is almost always asymptomatic and that is why we always incorporate blood tests and liver function tests into our workups.” —Dr Antonia

imAEs: Liver

Watch Scott Antonia, MD, PhD, medical oncologist and Chair of the Thoracic Oncology Department at the Moffitt Cancer Center in Tampa, Florida, discuss the diagnosis and treatment of hepatitis and related imAEs.

Video Chapters

“If we intervene early with steroids we often, and rarely, I would say, need to go to the next step that is higher-dose steroids with longer taper.” —Dr Cohen

imAEs: Lungs

Watch Ezra Cohen, MD, medical oncologist at the UC San Diego Moores Cancer Center, discuss the diagnosis and treatment of pneumonitis and related imAEs.

Video Chapters

“What we tell patients about skin reactions is that this tends to be one of the earlier side effects they may notice.” —Dr Cohen

imAEs: Skin

Watch Ezra Cohen, MD, medical oncologist at the UC San Diego Moores Cancer Center, discuss the diagnosis and treatment of rash, itching, and related imAEs.

Video Chapters

References: 1. Gangadhar TC, Vonderheide RH. Mitigating the toxic effects of anticancer immunotherapy. Nat Rev Clin Oncol. 2014;11:91-99. 2. Nishijima TF, Shachar SS, Nyrop KA, Muss HB. Safety and tolerability of PD-1/PD-L1 inhibitors compared with chemotherapy in patients with advanced cancer: a meta-analysis.Oncologist. 2017;22:1-10. 3. Postow MA, Callahan MK, Wolchok JD. Immune checkpoint blockade in cancer therapy. J Clin Oncol. 2015;33(17):1974-1982. 4. Weber JS, Yang JC, Atkins MB, Disis ML. Toxicities of immunotherapy for the practitioner. J Clin Oncol. 2015;33(18):2092-2099. 5. Kumar V, Chaudhary N, Garg M, Floudas CS, Soni P, Chandra AB. Current diagnosis and management of immune related adverse events (irAEs) induced by immune checkpoint inhibitor therapy. Front Pharmacol. 2017;8:1-14. doi:10.3389/fphar.2017.00049. 6. Spain L, Diem S, Larkin J. Complications of treatment: management of toxicities of immune checkpoint inhibitors. Cancer Treat Rev. 2016;44:51-60. 7. Cousin S, Italiano A. Molecular pathways: immune checkpoint antibodies and their toxicities. Clin Cancer Res. 2016;22(18):4550-4555.

X


X


X


X


X


X


X


X


X


X


X


X


X


X


X


X


X


X


X


X


X


X


X


X


X


X


X


X


X


X


X


X


X


X


X


X


X


X