Immune Checkpoint Inhibitors and Cardiotoxicity: An Emerging Issue

Over the years, cancer immunotherapies have revolutionized the clinical management of a wide spectrum of cardiotoxicity induced by anticancer drugs. In this video, Marielle Scherrer-Crosbie, MD, PhD, from the University of Pennsylvania, Philadelphia, goes into detail about immune checkpoint inhibitors, and some issues that have arisen recently.

Following is a transcript of her remarks:

Immunotherapy is a huge, I would even say, revolution in the treatment of cancer. It has been explored for already quite a few years where the idea of increasing the immune system of the patient in order to attack the tumors was floated. The first treatments had a lot of toxic side effects, and so there was a dip in this specialty, but more recently there have been huge advances, including the immune checkpoint inhibitors and also the targeted lymphocyte, the CAR T-cell therapies.

To start with, the immune checkpoint inhibitors, these have really, really improved the prognosis of some of the most aggressive malignancies, in particular, metastatic melanoma, metastatic renal cell carcinoma, non-small-cell lung carcinoma. There’s several classes of those immune checkpoint inhibitors. The most well-known of them are anti-CTLA-4, which ipilimumab is the most well-known of them against melanoma. Then the PD-1 inhibitors, of which nivolumab is the most well-known. Most recently, some anti-PD-L1 checkpoint inhibitors have also been developed.

Those checkpoint inhibitors basically enhance the function of T lymphocytes. There are side effects, which are well known, and more than 90% of patients experience those side effects. The cardiac side effects have been identified very recently, first as anecdotal cases and they are mainly myocarditis, although there are other side effects, cardiac side effects of those immune checkpoint inhibitors that have been identified and that are conduction abnormalities and decreases in left ventricular function that may not be myocarditis and also pericarditis.

The most well-known now because there have been some series reported in the literature is the myocarditis, which may occur maybe, although we’re not sure, in 1%, maybe even 2% of cases and can be fatal in 50% of patients. This is a real issue. There are two “larger series” that have been reported. We don’t really know the prevalence of those myocarditis because it’s only retrospectively that we have noticed them, and so maybe not every one of them is picked up. Things to know about them are severalfold. First of all, the troponin seems to be elevated in most of them. It depends on the series, but might be a good biomarker. The left ventricular ejection fraction is not always decreased, although an echo is recommended. It might not detect the myocarditis. The BNP might be elevated, which is another way to detect some abnormality of the cardiac function, obviously. MRI may also be useful in determining whether this is myocarditis, although may not be fully sensitive.

The treatment for this myocarditis consists on very high doses of corticoids. If that doesn’t work, then the second tier of immunosuppressors may be used and even a third tier. That is a very important issue in the immune checkpoint inhibitors. I think that we will see more and more and more work is needed, obviously, to know exactly what the prevalence of those complications is and to guide the clinician on how to detect, monitor, and treat those patients.

https://www.medpagetoday.com/clinical-connection/cardio-oncology/76970