Nurse Practitioner Lisa Kottschade Discusses Immune-Related Adverse Events, Biomarkers

Lisa A. Kottschade, RN, CNP, FAPO, discussed immune-related adverse events, which she presented on at The American Journal of Managed Care^®’s Institute for Value-Based Medicine^® event hosted by Minnesota Oncology in Minneapolis, Minnesota, on September 12. Kottschade, who is primarily interested in malignant melanoma treatment, also discussed the use of biomarkers.

Kottschade is a nurse practitioner at Mayo Clinic, chief operations officer at Midwest Melanoma Partnership, president of the Advanced Practitioner Society for Hematology and Oncology (APSHO), and an associate professor of oncology.

Transcript

What immune-related adverse events occur due to immune checkpoint inhibitors? What strategies can be used to manage them?

Immune-related adverse events are a direct result of a patient's immune system being overstimulated. I tell people to think of it as “everything-itis.” The 4 most common that we see are those that affect the skin; the GI [gastrointestinal] tract; endocrine, so like your thyroid; and the liver. They can affect any body part, body system, any organ. They can be life threatening, and there have been fatalities reported.

The best strategy that we can look at is early intervention. We don't really have a great way to predict who's going to have side effects and when. We do know that certain side effects tend to occur after a certain number of doses or at certain time points, but that's not a guarantee; some people will have those side effects way down the line, some people will have them earlier.

Really close communication with your treating oncologist [or] hematologist is important and that you report any side effects early. We really encourage that dialogue between patient and provider.

Can you please explain Mayo Clinic Rochester’s immune related adverse events initiatives?

My primary tumor focus is melanoma, so we were the first to have an approval with an immune checkpoint inhibitor. We were really at a loss when we first started treating these patients because the side effects were so much different than what we had ever used with traditional chemotherapy.

We developed strategies, and I mean we, the greater melanoma community as a whole, were the first to develop strategies on how to treat these. We were starting to see these immune checkpoint inhibitors cross other tumor groups. Kind of the next big one to come to market was in lung, and there are a lot more lung cancer patients than there [are with] melanoma. We were seeing a lot more toxicity, and I was getting a lot of “curbside consults.” People would walk down the hall and say, “Hey, I've got this side effect. What do I do with this?” type thing because there wasn't really a lot of published guidelines at first. This has kind of just honestly snowballed with all the other tumor groups coming on board. I’m pretty sure that almost every, if not close to every, tumor type has at least 1 indication for immune checkpoint inhibitors.

We built this out of necessity. We’re a big tertiary academic center, and we were seeing patients coming into the ED [emergency department], and the ED didn't know how to treat these, or they were being mistreated and sent home inappropriately. We were getting calls from all over the hospital about these patients.

We started both an inpatient initiative as well as our outpatient initiative because these patients are not patients who have this side effect and it goes away 3 to 5 days later, like with chemotherapy. These patients need long-term management, and that's where I got the idea to actually start this clinic. I also needed to have the input of our multidisciplinary colleagues from GI and endocrine because, again, these side effects were very foreign to us, and they mimicked other autoimmune diseases like Crohn [disease or] colitis. We involved all of our outside colleagues in this group as well to collaborate and have best practices moving forward for these patients.

In your bio on the Mayo Clinic website, biomarkers are listed as your special interest. Can you please explain how biomarkers work, specifically during malignant melanoma treatment?

There's a variety of biomarkers in any cancer type, and mostly what biomarkers are used for is either predictive values, so predicting who may respond to a treatment [and] who may not, [or for] monitoring. There are some biomarkers that you can use to monitor a patient while they're on therapy.

Unfortunately, in melanoma, we don't have a ton of really active biomarkers. We have mutational testing that we do to look at patients to see if they will respond to a different type of therapy that's targeted towards that mutation. We don't have a lot of biomarkers in melanoma.

One of the new, exciting things that is coming to melanoma, though, is circulating tumor DNA. There are several companies out there that are looking at that, and we're hoping that this is a way that we can look at patients who have minimal residual disease in a metastatic setting or they've had a complete response and we want to know if we should stop their therapy. We do serial blood draws to look for this circulating tumor DNA, and if it's not detectable then that may be a good indication that this patient is in in full remission.

One of the other predictive biomarkers that has been explored in melanoma is that of, who has a type of melanoma that is more likely to recur? There's several things out on the market, one of the biggest ones that's probably out there is Decision DX. This is not probably something that we use in a lot of patients, but there's a nice group of patients [for whom] we would like to know if they're at higher risk for recurrence after they've had surgical removal of their melanoma and should they receive adjuvant immunotherapy vs observation. We don't have all that data available, but that's one of the things that a lot of people are exploring and using some of this in clinical practice. Hopefully, there'll be some clinical trials around this so that we can better serve our patients and give patients who need treatment treatment and those who don't, we don't give them treatment.