Understanding Side Effects of Immune Checkpoint Inhibitors, with Tian Zhang, MD, MHS, and Afreen Idris Shariff, MD

November 1, 2021
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In this podcast, Dr. Tian Zhang and Dr. Afreen Shariff discuss common and sometimes serious side effects caused by a type of immunotherapy called “immune checkpoint inhibitors.” They also explain why it is important for people with cancer to track the side effects they experience and discuss them with their health care team.



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In this podcast, Dr. Tian Zhang and Dr. Afreen Shariff discuss common and sometimes serious side effects caused by a type of immunotherapy called “immune checkpoint inhibitors.” They also explain why it is important for people with cancer to track the side effects they experience and discuss them with their health care team.

Dr. Zhang is an associate professor of Internal Medicine at UT Southwestern Medical Center and is a medical oncologist at the Harold C. Simmons Comprehensive Cancer Center. She is also a Cancer.Net Specialty Editor.

Dr. Shariff is an endocrinologist and assistant professor of medicine at Duke University School of Medicine and the Associate Director for the Multi-Disciplinary Toxicity Program at the Center for Cancer Immunotherapy at Duke Cancer Institute.

Together Dr. Zhang and Dr. Shariff host a podcast called Checkpoint NOW discussing a multidisciplinary approach to managing side effects of immunotherapy. Learn more and listen at www.checkpointnow.org.

View full disclosures for Dr. Zhang and Dr. Shariff at Cancer.Net.

Dr. Zhang: Hi, everyone. Thank you for joining. My name is Tian Zhang, and I specialize in treating patients with kidney, bladder, and prostate cancers. I'm happy today to be joined by my wonderful colleague at Duke, Dr. Afreen Shariff.

Dr. Shariff: Hello, everyone. I'm Dr. Afreen Shariff, endocrinologist, assistant professor of medicine, and associate director at the Center of Cancer Immunotherapy at Duke Cancer Institute. We're happy to talk today on the podcast Cancer.Net about immune checkpoint inhibitors and associated side effects that many patients often are concerned about. Neither of us have any disclosures related to this podcast content.

Dr. Zhang: Thanks, Afreen. With the increase in use of immune checkpoint inhibitors for patients with cancer and the prevalence of side effects and toxicities, we thought it was important for patients to understand what side effects to monitor for and when to contact their doctors for further guidance and management. We thought we would put together this particular podcast to focus on side effect monitoring from a patient perspective.

Dr. Shariff: I agree. We have some side effects that can potentially be attributed to multiple toxicities, but there are others that can be pretty straightforward. These are times when referrals to subspecialists like myself are necessary. And at other times, the treating oncologist primarily manages toxicities. The more patients know, the better prepared they will be when starting on immune checkpoint inhibitors. Tian, let's get started. When you are introducing a new start for immune checkpoint inhibitors to a patient in your clinic, what is your overall advice?

Dr. Zhang: Afreen, I think it's so important for patients to understand the general scope of side effects to monitor for. These include rashes and diarrhea, which are more common and relatively straightforward to attribute, but also other nonspecific symptoms like fatigue. I start with an overview about common side effects of rash and diarrhea, discuss a little bit more about rare side effects of inflammation in the lungs or liver, and then talk about potential endocrine side effects. And we do that all when the patient's starting immune checkpoint inhibitors in my clinic.

Dr. Shariff: Oh, that's great, Tian. What should patients know about diarrhea?

Dr. Zhang: Sure. So diarrhea is reflective of inflammation in the colon, what we call colitis. And this can occur in mild form or in a more severe form and is 1 of the most common side effects of immune checkpoint inhibitors. Changes in stool caliber, particularly loose or watery stools, and also frequency per day should be quantified and noted. Diarrhea does not often have blood, but bloody stools are also possible and should be reported. If bowel movements while on checkpoint inhibitors increase to 2 to 3 times more per day above baseline, patients should start reporting these to their treating oncologists for further management.

Dr. Shariff: Well, I'm sure our audience and some of the patients on immune checkpoint inhibitors will find this very useful. Now, skin rashes are seen quite commonly as well. For patients being treated with immune checkpoint inhibitors, what would you like them to know about these rashes?

Dr. Zhang: Sure. Of course, skin rashes vary from mild to severe and treatment varies with the diagnosis. If patients notice blisters and pain, this can certainly be an emergency and needs to be evaluated further by their oncologist who may then refer them to a skin doctor for more treatment. Large patches of red rashes can also be concerning. In general, we start with topical steroids for mild rashes and then add on oral steroids if topical ones are not controlling the rash.

Afreen, we see fatigue so often in patients treated with immune checkpoint inhibitors. Can you share some insight into different side effects that can cause fatigue?

Dr. Shariff: Tian, this is a very important question and common concern expressed by many patients. Now, often it is difficult to identify the cause if fatigue occurs in isolation without any other symptoms. Now, fatigue can result from immunotherapy and from cancer itself. But what I want to emphasize is the difference between ongoing fatigue and profound fatigue, which is a severe version affecting everyday activity levels. When patients experience profound fatigue, it's important to know what other symptoms are present that can help with identifying a cause.

Dr. Zhang: Great. And what other symptoms should patients be aware of?

Dr. Shariff: Sometimes this occurs with headaches and vision changes, indicating a side effect causing inflammatory changes of the pituitary gland in the brain. If this is a concern, your oncologist will advise further testing and a referral to a hormone doctor like myself called an endocrinologist. Now, if fatigue occurs with rapid weight loss, increased heart rate, and tremors, these can be signs of an overactive thyroid called hyperthyroidism. Now, in contrast, fatigue with weight gain can indicate an underactive thyroid. Both of these thyroid-related side effects will require lab evaluation to confirm a diagnosis.

Dr. Zhang: Afreen, fatigue is so common and also a presenting symptom for diabetes, as well. Can you tell us more about this?

Dr. Shariff: Yes. Fatigue and weight loss are common in new-onset or worsening diabetes. With immune checkpoint inhibitors, you can see a rare side effect of insulin deficiency, which is called type 1 diabetes. It's a rare side effect and needs treatment right away. What makes the symptoms a little different is that this fatigue is seen with increased thirst and appetite and a high blood sugar, which helps with the diagnosis. Now, Tian, we also see fatigue with shortness of breath. Now, what side effects can cause this?

Dr. Zhang: When a patient comes in with shortness of breath, we're often thinking about heart and lung toxicities from immune checkpoint inhibitors. Measuring oxygen saturation helps. Sometimes patients who have inflammation in their lungs, what we call pneumonitis, will have decreased oxygenation levels. In the clinic, if patients report shortness of breath on exertion, we will also obtain EKGs, echocardiograms, and other labs to evaluate for heart dysfunction. And often, subspecialists will help us in managing lung and heart toxicities from immune checkpoint inhibitors.

Dr. Shariff: Excellent. Now, what other complications can we see in a patient treated with immune checkpoint inhibitors?

Dr. Zhang: Liver dysfunction is 1 that we haven't talked about yet, and liver dysfunction is often without symptoms. Oncologists will monitor liver function generally every few weeks when patients are treated with immune checkpoint inhibitors. An elevation from baseline will spark suspicion that the immunotherapy is responsible, or other drugs. And often we will involve a liver specialist. And if, due to the immune therapy, we'll often treat that with steroids.

Dr. Shariff: That's very helpful. Now, what about other toxicities like kidney toxicity and toxicities to the nervous system?

Dr. Zhang: Sure. Certainly, these are rare forms of toxicities, the ones that affect the kidneys or neurologic toxicities. But they can certainly happen. For kidney toxicities, we would monitor kidney function on labs and sometimes would need to involve a kidney specialist. These are often primarily treated with steroids. Neurologic toxicities are rare but can be disabling and dangerous if diagnosed late. So patients can experience symptoms ranging from mild, like numbness and tingling, to more severe symptoms of weakness and paralysis. These situations often involve the input of a neurologist.

Dr. Shariff: Thanks, Tian, for your insight on these rare side effects. Interestingly, some side effects may be picked up on labs while patients may not have any symptoms. This is why oncologists are often checking blood work with every treatment. And it's important to bring up symptoms when you do experience them while on treatment. While these side effects are concerning, it's important to have a conversation with your treating oncologist to weigh your risk for each of these side effects. Most importantly, remember that a majority of these less severe side effects are manageable and do not need interruption of immune checkpoint inhibitors. This is a general guidance, and it's important to always refer to your treating clinician.

Dr. Zhang: Thanks, Afreen. I hope this session helps bring awareness for symptom management and side effects management for patients on immune checkpoint inhibitors. For other information on specific toxicities, there are several resources. You can follow us on Twitter at CheckpointnowMD, check out our podcast, Checkpoint Now, on Apple Podcast or Spotify, or also go onto the Cancer.Net website with more information on disease-specific treatments and toxicities.

ASCO: Thank you Dr. Zhang and Dr. Shariff.

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