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Dr. Saba:
Hello, everyone. This is CME on ReachMD, and I'm Dr. Nabil Saba, and here with me today is my colleague and friend, Dr. Barbara Burtness.
And Barbara, let's start with a case vignette. We have a 65-year-old male who comes in 1 year after completion of concurrent therapy for HPV-related disease. He’s enrolled on a clinical trial and ended up being randomized to the control arm of single-agent PD-1 inhibitor. Two weeks after initiation of therapy, he presents with shortness of breath and a clinical picture of diabetic ketoacidosis. He had a cardiac evaluation with evidence of an acute infarct, elevated troponins, yet no evidence of coronary obstructive disease. His pembrolizumab was discontinued, and he was started on steroids which resulted in normalization of his troponins.
What is your impression of this case and can you comment?
Dr. Burtness:
Yeah. Well, so I think immune checkpoint inhibitor-related myocarditis and cardiac vasculitis are extremely rare complications. We have often used cardiac MRI as both a diagnostic tool and to follow as patients are tapered off their steroids or other immunosuppressive regimens. And, you know, it sounds like this patient did well with discontinuation of pembrolizumab and beginning steroids.
We are routinely getting a cardiogram and baseline troponin so that, if in the rare event that this presents, we have some comparator, but I think it's important to remain alert to it to understand that it can happen. On the other hand, it’s been quite rare in my experience.
Dr. Saba:
Yeah, great, great points. You mentioned your practice of getting cardiac evaluation at baselines. Can you comment about the general immune-related adverse events and how common these are and mention also, briefly, how you manage these?
Dr. Burtness:
Yeah, sure. So what I tell my patients is that the majority of people are going to feel a little fatigue, that a low-grade rash is not uncommon. But the high-grade toxicities, the ones that lead to treatment discontinuation and mandate steroids or might land somebody up in the hospital, those happen in about 17% of patients. And then I list about 17 different organ systems that might be affected. And, you know, I think that it's true that pneumonitis and diarrhea are a couple of percent and then there are a number of other rarer things. The rheumatologic complications can often take a number of months to present. We keep a close eye on patients; we have them educated about what to keep an eye out for. If it's something that only appears on scans or lab work and the patient's completely asymptomatic, I think you can keep going forward. If it's a mild symptom, the patient's symptomatic but it's not life-threatening, doesn't mandate intervention, then we'll hold the pembrolizumab and observe. And it's for grade 3 toxicity, where the patient's short of breath or coughing or requires oxygen and has diarrhea. It’s uncommon to see hematologic complications, but if they're requiring transfusion or whatever, those are the situations where we begin steroids, where we follow the patients very closely, sometimes hospitalize them. If there's no response to steroids within 7 days think about mycophenolate or infliximab or something like that. If the patient's responsive to steroids, which the overwhelming majority of them are, we begin the taper after 1 week and try to taper over a month.
Dr. Saba:
Well, great insights, of course, for a topic that affects many of us. I think it's important also to stress the multidisciplinary team and its role in identifying these and spreading the word because, believe it or not, when we had a myocarditis recently, our cardiologists were not actually very astute to the existence of this. And so we wanted to just make sure that these that this information is commonly available to everyone.
And so in summary, I would say being familiar with the immune-related side effects is very important when using these drugs in any malignancy, including head and neck cancer. And the common side effects, as you mentioned, include hypothyroidism, manageable side effects. But a number of side effects are difficult to manage and are serious, and certainly, cardiac side effects and neurologic side effects, those, in general, we would not, in general, rechallenge with immunotherapy if these happen.
In conclusion, I would say this has been an abbreviated great discussion. But unfortunately, our time is up and thanks for listening.
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