Expert oncologists discuss the management of immune-related adverse events in renal cell carcinoma.
Elizabeth Wulff-Burchfield, MD: To build on what you just were talking about with regard to endocrine toxicities, I’ll carry on the case discussion briefly here. With this patient, she had a partial response at 4 months after initiating nivolumab and ipilimumab, which is great to see. During cycle 9, she ended up having quite a downturn in her quality of life with fatigue, weakness, and weight gain. Her work-up showed that she had low free T4 [thyroxine], low TSH [thyrotropin], but did not appear to have hypophysitis. So this individual was treated with repletion, essentially. And from this case description, it sounds like the nivolumab was held when free T4 was in the normal range.
To build on some of what’s been discussed about immune-related adverse events [IRAEs], I’d love to hear from you, Dr McKay, about these folks who are receiving immunotherapy [IO], which, thankfully, almost all of our patients can safely receive these regimens up front. Do you have any particular pearls you impart upon patients, caregivers, or your team? Any strategies your institution or practice has to either mitigate, screen for, or counsel patients regarding immune-related adverse events?
Rana McKay, MD: Absolutely. I think this is where we integrate with our nursing team, MA [medical assistant] team, and other consultants across the hospital. I think it’s about providing really clear education to the patients, providing clear ways that patients can get in touch with us if they have symptoms. I’m very clear, [I tell them] the after-hours number and the weekend number. “If you’re having anything you’re not sure about, call us.” I basically tell them,
“Name the organ and add itis to the end of that organ, and it can happen there. And we can’t predict if you’re going to get it or not.” So I think it’s that education that’s really important.
The other thing is that we have tremendous education for our MA staff, LVNs [licensed vocational nurses], nursing, and APPs [advanced practice providers]. These patients call in, they may call not to say a generic line, but a more general pool where they’re just getting triaged. [They may tell us they have] a bit of diarrhea, and they minimize their symptoms. A bit of diarrhea is actually 6 large watery bowel movements per day, which is pretty concerning. So I think we do a lot of education around making sure you look up the drug that the patient is taking, go into the treatment plan and see what they’re on, go into their medication list and see what they’re on, confirm with the patient what they’re on, and quantify things. Even though CTCAE [Common Terminology Criteria for Adverse Events] grading is for trials, we do use it to help with our risk management in the clinic to assess severity of symptoms. We do a lot of education for our nurses, who do a lot of the education, [and for] our APPs.
On the ED [emergency department] side here, our institution has implemented a measure where if somebody is receiving an IO therapy and received it within a certain time window, there’s acknowledgement. This [screen] pops up when you log into that patient’s chart [stating] this patient has received immunotherapy within X, Y, Z days, and you have to acknowledge it. I think that’s also been helpful. I definitely lean on my colleagues from other disciplines, particularly GI [gastrointestinal], neurological, and certainly cardiology. I think those are the big ones. Sometimes dermatology too, we’ve seen some lichenoid and other dermatologic conditions that can be a bit difficult to manage. I think having that support structure is really important for AE management.
Pedro Barata, MD: If I may add something really quick, I agree, and I would say the management changes quite a bit. For instance, for thyroid alterations, commonly we don’t hold immunotherapy, we control the thyroid changes and we keep going. And for the most part, we are successful with that approach. It would be different on this particular case, as an example.
The other thing has been an effort to put together this immune-related adverse event tumor board at different hospitals. That has been great because one thing that some of us encountered, and of course everybody’s busy, everybody has their own organization within their own sections, [but we] get a fast track. I need fast-track access to endocrinology or rheumatology, etc. Sometimes the way to do that is to find a time that we can all sit at the same table. That’s not easy and it’s not across the board, but finding the go-to when these situations happen I think is very relevant.
The other thing is, as the electronic medical records are integrated, I think it’s pretty important because a lot of times patients end up in the emergency [department], and if you don’t educate [the ED staff] that they are on these therapies, a lot of times some of the immune-related adverse events are missed. They’re being called something else. Then it’s a completely different way that those patients are treated because there’s lack of awareness of what these checkpoint inhibitors do. So I think there’s work to do from that perspective. Not just grand rounds, internal medicine, etc., but there’s a lot that can be done to optimize it.
The last thing I was going to say about this is there are a number of guidelines about this. ASCO [American Society of Clinical Oncology] has fantastic guidelines on how to manage some of the common immune-related adverse events, like diarrhea. Having those handy helps, in addition to CTCAE, to understand that we have to identify those problems as soon as possible and then intervene appropriately. Guidelines like ASCO on those topics are helpful from the diagnosis piece, but also to the treatment piece.
Elizabeth Wulff-Burchfield, MD: They’re crucial. I can’t even tell you how often I end up pulling them up because I want to make sure I’m looking at them every time. Dr McKay, to your point about grading the adverse events, I couldn’t possibly feel stronger about that. I was trained to grade every symptom, every time, in every note. I do that routinely even for folks who aren’t on trials. That may make me a bit twisted, but it does help ground me in the criteria to make sure that I am not either over- or underestimating something. To the point about resources, Dr Barata, I think ASCO needs to make an IRAE tumor board, like they have molecular tumor boards. This is a call to action to make it happen. It would benefit so many people because getting someone into endocrinology in a lot of places, including where I practice, is really hard.
The only other thing I was going to mention was that, I serve a large rural population, and a lot of times folks cannot get to where I practice if they are having potentially immune-related [adverse] effects. Some of the things I emphasize in addition to what you all have said is, “Call me first, every time.” I basically tell them, “You don’t need to know what the symptom is from. In fact, do not try to figure out if what you’re going through is from your treatment or not.” Just don’t do it because it creates this paralysis by analysis moment for the patient, and sometimes they don’t want to call. So I just basically tell them, “If you’re experiencing anything unpleasant for more than 1 day, and it’s not something you’ve experienced before your cancer, I need a call. I will take responsibility for telling you if it’s important or not.”
The last thing I was going to say is in terms of resources. The Hematology/Oncology Pharmacy Association, HOPA, which is also associated with BCOP [Board Certified Oncology Pharmacist], has some great handouts that I love to give patients about what immunotherapy is and how it works. They have little cartoons. I give those to every patient every time because I think they’re much better than printing out resources that just list every potential adverse event from the package insert. Also, it’s possible to get wallet cards that basically say, “I am on immunotherapy,” the way that they have for their stents or for their ports. So I think for folks who particularly who may not live immediately in the area where your institution’s ED is, I would strongly recommend something like that, because how many times have we gotten a note back from an ED that says, “The patient’s on chemotherapy for kidney cancer and comes in with diarrhea?” Emphasizing that it’s not chemotherapy is so important.
Transcript edited for clarity.