Considerations for the Use of Steroids: Management of irAEs Guideline (Part 13)

An interview with Dr. Leslie Fecher from the University of Michigan Health System, author on “Management of Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy: ASCO Guideline Update.” She reviews considerations for the use of steroids to manage immune-related adverse events in patients treated with immune checkpoint inhibitor therapy in the final episode of this 13-part series. For more information visit www.asco.org/supportive-care-guidelines   TRANSCRIPT SPEAKER: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care, and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. BRITTANY HARVEY: Hello, and welcome to the ASCO Guidelines podcast series, brought to you by the ASCO Podcast Network, a collection of nine programs covering a range of educational and scientific content, and offering enriching insight into the world of cancer care. You can find all the shows, including this one, at asco.org/podcasts. My name is Brittany Harvey, and today we're continuing our series on the management of immune-related adverse events. I am joined by Dr. Leslie Fecher from the University of Michigan Health System in Ann Arbor, Michigan, author on Management of Immune-Related Adverse Events in Patients Treated with Immune Checkpoint Inhibitor Therapy: ASCO Guideline Update, and Management of Immune-Related Adverse Events in Patients Treated with Chimeric Antigen Receptor T-Cell Therapy: ASCO Guideline. And today we're focusing on considerations for the use of steroids to manage immune-related adverse events in patients treated with immune checkpoint inhibitor therapy. Thank you for being here, Dr. Fecher. LESLIE FECHER: Thank you, Brittany, for this invitation. BRITTANY HARVEY: Great. Then I'd like to note that ASCO takes great care in the development of its guidelines and ensuring that the ASCO conflict of interest policy is followed for each guideline. The full conflict of interest information for this guideline panel is available online with a publication of the guidelines in the Journal of Clinical Oncology. Dr. Fecher, do you have any relevant disclosures that are related to these guidelines? LESLIE FECHER: The details of my disclosures are included in the manuscript, but I'd just like to note that I have received research funding, specifically in the form of clinical trial funding, from companies that do manufacture these immunotherapies. BRITTANY HARVEY: Thank you. Then getting into the content, so steroids are valuable agents in the management of immunotherapy-related adverse events. So first, what should clinicians consider pretreatment with steroids? LESLIE FECHER: So I think one of the first things is obviously going back to the traditional history and physical exam, and making sure you understand any preexisting comorbid conditions, such as diabetes, high blood pressure, preexisting cataracts or glaucoma, infections, osteopenia, or osteoporosis. It's always good to try and optimize things before getting started on steroids. Additionally, it's typically considered very reasonable to check hepatitis B and C serologies prior to starting immunotherapy treatment. And also consideration of assessment for tuberculosis, if there are specific risk factors, understanding if somebody already carries a diagnosis of HIV, and understanding the status of that in advance would be relevant. BRITTANY HARVEY: Those are important considerations. Then in addition to that, how should opportunistic infections be prevented? LESLIE FECHER: So one of the most common infections that we tend to try and prevent is pneumocystis jirovecii pneumonia, or PJP, previously known as PCP pneumonia. And this is one of the more common things that we recommend prevention for. So in patients who have received the equivalent of prednisone dosing of 20 milligrams per day for four or more weeks, or greater than 30 milligrams per day for three weeks or more, that's when it would reasonably be indicated. There are obviously specific institutional guidelines for the preferred regimen, but I think that's important to consider. The role of viral prophylaxis as well as antifungal prophylaxis is a bit less clear, but is something to be considered, especially depending on the duration of the steroid course. And whether or not in the setting of herpes zoster, for example, if the patient has had issues with zoster in the past. BRITTANY HARVEY: OK. and then the use of these steroids is to treat immunotherapy-related adverse events. But what are the key recommendations for monitoring both the short-term and long-term adverse effects from steroids? LESLIE FECHER: So I think being aware of the side effects as well as making sure that the patients and the family members or loved ones that are helping them are aware of them as well. From a short-term standpoint, typically we recommend things such as GI prophylaxis, with either a proton pump inhibitor or a histamine 2 antagonist, to reduce or prevent gastric ulcers or duodenal ulcers, or gastritis. Given some of the long-term effects, such as bone loss as well as steroid myopathies, we encourage exercise as well as physical therapy in some circumstances. But really one of the most important things is to make sure that you're constantly both assessing and eliciting from the patient and family members for any other side effects. So often, common acute short-term side effects can be increased risk of infection. So making sure you're asking about it. They may not have the typical manifestations of infection, such as fevers or chills. insomnia or difficulty with anxiety, irritability, skin changes for sure, or high blood pressure. And then obviously being aware that laboratory evaluation for glucose intolerance is important as well. BRITTANY HARVEY: Definitely. Those are important points for clinicians, patients, and caregivers. So then we've had some of the other authors on this guideline talk about tapering steroids. So what are those recommendations on how clinicians should taper steroids? LESLIE FECHER: So tapering is an art in and of itself in my opinion, and there's lots of different ways to do it. Some general concepts are you want to really try and understand what the side effect is that you are managing, because that will require frequent reassessment. And so when we talk about reassessing patients during the treatment of their toxicities, the management of the toxicities, in my opinion, is almost as important as the management of the immunotherapy itself. And so patients still need to be seen, still need to be assessed, still need blood work done. And so reassessment for the toxicity that you're managing, given that we can see rebounding of symptoms. So for example, if they were getting treated for diarrhea or colitis, having a really good understanding of what their baseline bowel movements were, how bad they got, and then a constant reassessment and making sure that the patient, as well as the family, knows that this should not come back again, if you will, in the midst of the taper. I think the other things to be aware of is that I tend to always reassess before giving the next decrease in dose of the steroids rather than having an automatic decrease. Because again, patients sometimes will follow those, even if their symptoms recur. So ensuring that there's that, again, reassessment. When we're on oral steroids, some of the general concepts we say is that the course should be at least usually about four weeks total, sometimes as long as six weeks or even longer, depending on the toxicity. And we think about, on average, decreasing from a prednisone or prednisolone amount roughly 10 milligrams every three to seven days, depending on the side effect that you're managing. The longer the taper, the slower you might need to go, depending at the end. And also being aware of the risk of adrenal insufficiency towards the end of a long steroid course is also an important thing to assess for. BRITTANY HARVEY: Great. I appreciate you reviewing those considerations. So then in your view, Dr. Fecher, how will these recommendations for the use of steroids in the management of immune-related adverse effects impact both clinicians and patients? LESLIE FECHER: I think it will bring ongoing awareness to the physician and their team, as well as the patient and their team. I think that this is obviously really important that everybody is involved and aware. And I use the term engagement from a patient and family member standpoint. It's really critical to have an understanding of the side effects, have an understanding of the prednisone management. And explaining that not only to the physician team and nurses and other people involved in their care, but when patients call in, that they know to look out for rebounding of their symptoms and to report them immediately, as that can impact steroid tapering. I think, again, the awareness and engagement is going to ensure that patients get the best care and best results. BRITTANY HARVEY: Absolutely, and thanks for highlighting both that awareness and engagement. So thank you so much for your work on these guidelines, and for taking the time to speak with me today, Dr. Fecher. LESLIE FECHER: Thank you so much, Brittany. I appreciate your time. BRITTANY HARVEY: And thank you to all of our listeners for tuning in to the ASCO Guidelines podcast series. To read the full guideline, go to www.asco.org/supportive-care-guidelines.  You can also find many of our guidelines and interactive resources in the free ASCO guidelines app, available in iTunes or the Google Play store. If you have enjoyed what you've heard today, please rate and review the podcast, and be sure to subscribe so you never miss an episode.