IKCS 2019: Immune-Related Adverse Events: An Interview With Dr. Mehmet Asim Bilen
Dr. Mehmet Asim Bilen of Emory University School of Medicine led a session at IKCS last month on the diagnosis and management of immune-related toxicity and later continued the discussion with PracticeUpdate.
PracticeUpdate: Dr. Bilen, you moderated the session regarding the diagnosis and management of immune-mediated toxicity. What are the most common immune-related adverse events seen in clinical practice?
Dr. Bilen: We had a very successful session at the IKCS meeting about immune-related adverse events. I think this is a very important area in medical oncology, particularly immune-oncology, since we are using checkpoint inhibitors in our clinical practice across multiple different tumor types. Currently, the most common immune-related adverse events seen in clinical practice are dermatologic, such as skin rash or various other types of skin involvement, pneumonitis, colitis, hepatitis, nephritis, different endocrine-related events such as hypothyroidism or hyperthyroidism, and various neurologic-related adverse events such as encephalitis. Cardiac-related immune adverse events can also be seen.
PracticeUpdate: What immune-related adverse event are most likely to lead to serious and potentially life-threatening consequences?
Dr. Bilen: When we treat patients with immune checkpoint inhibitors, GI, cardiac, and neurologic immune-related adverse events can lead to a serious outcome. In terms of GI, hepatitis or colitis are very important to diagnose and treat as soon as possible. In terms of cardiac, myocarditis has a very high mortality rate, over 50%, and I think that this is one of the most important immune-related adverse events that we need to treat in as timely a fashion as possible; most of the time we work with a multidisciplinary team, including cardio-oncologists. In terms of neurologic, myasthenia gravis and encephalitis need to be on the differential, and, again, multidisciplinary care is really important for those patients, including care from an expert neurologist, in terms of management and long-term follow-up.
PracticeUpdate: To your knowledge, is there a relationship between immune-related adverse events and response to immunotherapy?
Dr. Bilen: That is a very important question, and an evolving area of research in our field. Several retrospective series have been reported that address this question. For example, an analysis recently published in JAMA Oncology found a better response rate in patients with advanced non–small cell lung cancer treated with a checkpoint inhibitor who developed an immune-related adverse event. We looked at this question in patients who received immunotherapy in a phase I clinical trial and found that patients with grade 3 or higher immune-related adverse events had an improved overall response rate and longer median time to progression. We need to investigate this question in larger databases. In addition to that, we still need to understand each of those different immune-related adverse events since the underlying biology likely is different, and this needs to be considered in our analysis.
PracticeUpdate: At what time point during treatment do immune-related adverse events tend to occur?
Dr. Bilen: In clinical practice, when we use immune checkpoint inhibitors such nivolumab and ipilimumab, we tend to see immune-related adverse events early on during the first four cycles when we administer the combination treatment. Having said that, there are anecdotal cases that experience immune-related adverse events many months after initiation of therapy. In addition, we don't have any biomarkers to predict any of those immune-related adverse events. Because of this, treating providers need to be alert all the time when they use those agents.
PracticeUpdate: Immune-related adverse events can be hard to differentiate and manage. What are your general recommendations to the community oncologists and physicians who may come across a patient with an immune-related adverse event?
Dr. Bilen: This is a very, very important point. I completely agree that immune-related adverse events can be very difficult to diagnose and manage. Based on my experience, when those agents received initial FDA approval and became available as a center of care, it took some time for oncologists to become familiar with them. All of us had a learning curve; but, now, most oncologists are more familiar with what to look for. In addition to oncologists, primary internists also need to be familiar with those adverse events since most of the time they may handle those patients in the first place.
We also realize that patients who develop immune-related adverse events need multidisciplinary care since they may end up with multiorgan involvement. Because of this reason, in large academic centers, we work with expert consultants to help us to manage those cases, such as cardio-oncologists, endocrinologists, dermatologists, hepatologists, et cetera. We work as a team to diagnose, treat, and follow those patients since most of the time they are also followed as outpatients. I recommend that community oncologists establish a similar structure in their practices. Of course, we are happy to help them, to answer any questions, since most of the time those are complex cases.
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