Managing Immunotherapy Side Effects in MBC: The Importance of a Multidisciplinary Approach

Fatima F. Cardoso, MD; Hope S. Rugo, MD, FASCO; Rebecca A. Dent, MD; Zoe E. Quandt, MD, MS


June 16, 2023

This transcript has been edited for clarity.

Fatima F. Cardoso, MD: Hello, and welcome to this commentary on immunotherapy side effects and the need for multidisciplinary care. My name is Fatima Cardoso. I'm a medical oncologist. I'm based in Lisbon, Portugal.

I'm joined by my friends and colleagues, Drs Hope Rugo, Rebecca Dent, and Zoe Quandt. I will ask each of you to please give a short introduction of yourself.

Hope S. Rugo, MD, FASCO: I'm Hope Rugo. I'm a breast medical oncologist at the University of California San Francisco's Comprehensive Cancer Center, and I'm very interested in immunotherapy as a treatment but also in identification and management of toxicity, and have focused much of my recent interests in this area. Excited to be here!

Rebecca A. Dent, MD: My name is Rebecca Dent and I'm thrilled to be on this panel. I'm a medical oncologist at the National Cancer Center Singapore, and also chair of the Division of Medical Oncology. I have a great interest in triple-negative breast cancer; hence, we've been experimenting, we'll say, with immunotherapy now for almost a decade. I'm really excited to share some of our experiences today.

Zoe E. Quandt, MD, MS: My name is Zoe Quandt. I'm also at University of California San Francisco. I'm an endocrinologist with a focus in onco-endocrinology and a physician scientist in this same area. I'm excited to be joining you all to talk more about the endocrine side effects of immunotherapy.

Reorganizing Care

Cardoso: Thank you. We will start with addressing this need for multidisciplinary care. How much did you have to reorganize care for breast cancer patients since we started using immunotherapy?

Here, in our institution, we just started using immunotherapy about 1 or 2 years ago for breast cancer, and that meant reorganizing the care for these patients regarding support from other specialties.

Rebecca, what happened in Singapore when you started using immunotherapy for breast cancer, since you have many more years of experience?

Dent: My experience goes back about 15 years. I was a melanoma doctor in my other life in Canada. We first started using combination immunotherapy. I got very used to being a little more proactive and worried about patients because the side effects we see are much different from what we see with chemotherapy.

When I moved to Singapore and we started using immune checkpoint inhibition in clinical trials, one of the things one of my colleagues did was get some of our juniors very quickly to identify specialists, including endocrinologists, GI, and skin — with endocrinologists, of course, being first and foremost — maybe mid-career, who were really interested and could engage and help us because the problems that we saw were unique. They weren't typical problems. We had to work — and we continue to — very closely to try to distinguish how much is potentially a toxicity from chemotherapy vs the cancer vs immunotherapy.

I would say the time interval is so different from what we're used to using or what we're looking at that we were really learning together. This included an open dialogue, continued discussion over WhatsApp, monitoring people's symptoms, knowing how to taper steroids, learning how to diagnose; how to identify the toxicity, treat the toxicity, monitor it over time, and then decide whether to rechallenge.

It's not a one-time engagement; it's an ongoing relationship that, to be honest, for the most part, we aren't used to having. I think we both have found it quite fruitful and really critical to helping manage patients. Now, some of my colleagues in private practice don't have the same access to multidisciplinary care within one center but similarly have identified their key specialists that they're just used to collaborating with, and I think that makes all the difference.

Cardoso: Hope and Zoe, since you are working in the same institution, what is your experience?

Rugo: It's great that we were able to include Zoe for her comments here because that's what's so important for us. We're used to talking to our consultants about getting a biopsy or complications of cancer, but in this situation, we really needed to have urgent communication with specialists who we might not have previously needed to have that direct line with.

Then we needed to understand who was interested in this area, who had experience with it, and who would be able to give us information about getting the testing and then see the patient in a fairly rapid time period. What was interesting for me was the first patient I had with significant immune toxicity had colitis, and this developed almost 4 months after her last of two doses of checkpoint inhibitor.

We really didn't recognize that. This was many years ago. It was really a lesson, I think, for me about the importance of being able to have everybody in my team, including the breast cancer doctors, the nurses, and the triage nurses, be aware of the risks and then being able to immediately connect with a specialist even for blind biopsies for how to diagnose adrenal insufficiency.

We still don't really understand that on the oncology side, so we need to reach out to our specialists. We really have developed a team of people that we can connect with. Mostly, I would say GI is still the largest challenge, but for some of the rare toxicities we maybe don't have as good a connection, but we can always find somebody rapidly who can see the patient.

This is really important. On our end, we have to also have a very high degree of suspicion so that we know when we should be reaching out.

Zoe, your experience in this has been becoming our right-hand person for the diagnosis and management of endocrine toxicities. At UCSF, that was really a new function when you came to join us.

Quandt: People go into endocrine because there are no emergencies, but with checkpoint inhibitors, that's almost changed, right? We have to see patients much faster because the disease is progressing faster. I think that's one piece, that having the experience really helps with being able to monitor things in a different way than we traditionally do as endocrinologists.

The other thing that's really helpful, in that almost every patient I see is on an immunotherapy regimen, is that I'm used to the drugs and I'm used to knowing what's happening for the patients from their cancer perspective. I, of course, always defer to the oncologist but I have that familiarity with what is going on with them, with the rest of their lives. I think that adds to their care.

The Importance of Careful Monitoring

Cardoso: Now that you mentioned the monitoring, I think that's something that still people get a little bit — I wouldn't say confused — but do not yet fully understand what has to be monitored intensively and what can be monitored less intensively. There are guidelines, of course. There are ASCO and ESMO guidelines.

Is there any quick indication for those who are listening in terms of what you consider is mandatory before starting immunotherapy, immune checkpoint inhibitors, and while on therapy, from an endocrine point of view?

Quandt: There are three main toxicities that we see: thyroid, diabetes, and adrenal insufficiency from hypophysitis. Thyroid happens the most. I think most people will measure thyroid function tests with each infusion. Sometimes people will do it with every other infusion. Depending on the distance between the infusions, that can be okay.

The second you see anything abnormal, making sure that they go to every infusion if they're on 6-week intervals, having something in between those two infusions is important. We really want to try to catch people when the free T4 has fallen and the TSH lags. Sometimes that will not be elevated yet and we still have an interval of time to start therapy before someone's actually become overtly hypothyroid.

For diabetes, which is super-rare — we think it's probably less than 1% of the time in breast cancer patients — I love having an A1c before someone starts therapy, and then glucose with each set of labs is all that we really ask for.

For adrenal insufficiency, it depends on the trial that we're working on. With I-SPY, we actually check very frequently. In the practice that we have in other settings, it's less frequent. As we mentioned, it's one of the harder ones to diagnose. We can talk a little bit about that.

I think, at a minimum, any symptoms that can be related to adrenal insufficiency — so we're thinking about fatigue, loss of appetite, joint aches and pains, muscle aches and pains, nausea — those are all red flags in my mind that we should proceed with adrenal insufficiency diagnostic testing.

The other thing that's particular to the breast cancer population that we're treating is we often are giving immunotherapy before going to surgery. We really need to think about whether we need HPA axis testing before surgery, which is going to be thought of as a very stressful event and can actually induce an adrenal crisis.

Dent: We've treated many neoadjuvant patients over the past 5 or more years, part of KEYNOTE-173, KEYNOTE-355, and now on practice as well as some other preoperative studies for ER-positive breast cancer. It seems like a large amount of work to do with the TSH testing every cycle and the adrenal insufficiency workup. To be honest, I think it's really important in these curative patients going for surgery.

I also have made a habit of calling the anesthetist and the surgeon, reminding them that the patient is on immunotherapy, should they have any issues with blood pressure management post-op, because they sometimes think I'm crazy. Having seen some of these toxicities at other sites and how scary this can be, I don't think it takes much just to say, "Hey, just letting you know the patient is on immunotherapy. This is something you should look out for," because you're not going to be around when they're post-op at night or something happens. This is rare but it's quite significant [so it's important for me to consider in patients who are having surgery].

I think the thing about the thyroid is that this can happen at any time. Everybody's course of thyroid dysfunction, I've learned, just takes some experience, seeing many of these patients. Over time, some fizzle out slowly and some get worse very quickly. I don't think we can predict for which of those patients it is. We just have to learn to get used to it and connect with you so that you can keep on top of it, as you said.

Rugo: There are several important points about this. One fascinating patient that we had recently, that Zoe and I shared, was a woman who was on our I-SPY2 neoadjuvant trial using a checkpoint inhibitor along with an antibody-drug conjugate. The patient was using a steroid mouthwash, which she dutifully started 3 days before her first infusion.

Her cortisol came back halfway through at less than 1. We looked back and her first cortisol level was really low even before she started therapy, around 2, which is very unusual for most patients.

It turned out that, even though she swears that she was not swallowing the steroid mouthwash, when we reduced the frequency of use, her cortisol increased. She's the only person I've ever seen like that.

It was really helpful to consult with Zoe, who recommended a cosyntropin stimulation test, and although she didn't stimulate normally, she did stimulate. It's just fascinating to see that you can really misdiagnose these complicated toxicities and then commit people to lifelong steroids. It is critical that, as providers, we understand these intricacies of diagnosis.

On the other hand, one of my patients on our neoadjuvant trial for triple-negative disease went back to her health maintenance organization hospital for her surgery. Because we mandate that patients have a cortisol before surgery, she had her cortisol 2 weeks before surgery. It was less than 1 and she really did have adrenal insufficiency. She was evaluated by endocrinology and placed on steroids

When I saw her post-up (with a pCR), she said, "It was so funny; after that last cycle of chemotherapy" — which was paclitaxel, carboplatin, and pembrolizumab— "I felt so terrible. I was having nausea, I felt weak, and I couldn't do anything."

Of course, this was due to her adrenal insufficiency, and her symptoms rapidly resolved with replacement. We've seen this occur late after completing immunotherapy, as Rebecca pointed out.

Best Practices in Addressing Side Effects

Cardoso: Yes, and in fact, that's a common characteristic of many of these side effects. They can happen after quite a large number of cycles and even after stopping the treatment. I think that's a very important message to give not only to those who manage these patients, but also to those who don't, who are not so familiar with these treatments.

Recently we had a patient who had already stopped immunotherapy and had an important hepatitis. If you don't think that it can be related to something that was stopped 2 months ago, then you may miss out on the proper management.

Rugo: I think that's so fascinating because we diagnosed somebody with adrenal insufficiency also at another hospital, where the insurance mandated she receive her treatment there. I heard from a friend of the family that she was doing terribly at 3 months post-surgery, losing weight and unable to work. Turns out, she had adrenal insufficiency, which she had the labs to support, but nobody had really understood it at her hospital.

One question for Zoe. One thing that we sometimes struggle with on the oncology side is we see these TSH levels less than 0.01 and a T4, T3 that are elevated — so, thyroiditis, essentially, hyperthyroidism. We don't treat hyperthyroidism. The question is, how worried should we be about that? How do we manage those labs when they come back? Hypothyroidism is much easier.

Quandt: The hyperthyroid phase of what almost always will progress into overt and permanent hypothyroidism is really symptom driven. If someone is very uncomfortable in that phase, we start beta-blockade.

Honestly, most patients tolerate it pretty well. I have had one case, an older gentleman — not a breast cancer patient, but an older gentleman. He had cardiac issues and atrial fibrillation. He ended up needing a thyroidectomy because we were unable to control his atrial fibrillation with rapid ventricular response using our traditional methods. We ended up starting all the things for hyperthyroidism that we knew weren't likely to work in this setting, but just because we were trying to avoid surgery.

Certainly, if someone is super-symptomatic or cannot tolerate that tachycardia, we have other approaches. In general, we're able to just sit tight, treat that tremor and anxiety with beta-blockade, and keep monitoring for the switch to hypothyroidism.

Cardoso: Do you commonly see Graves disease, for example?

Quandt: Graves disease itself is super uncommon. We're working on a case report of Graves ophthalmopathy. If the hyperthyroid phase lasts greater than about 6 weeks, I'll start testing for the antibodies for Graves disease. I've never seen it besides this one case.

Cardoso: Rebecca?

Dent: I've had quite a few patients with thyroid dysfunction. I would agree. We just monitor them, but nobody's really needed treatment for hyperthyroidism. It really does seem to taper off quite quickly. When to start initiating therapy in the hypo phase, I find, varies quite a bit.

Special Considerations During Treatment

One thing I wanted to ask the panel is that quite a few patients take probiotics, proton pump inhibitors (PPIs), antibiotics, and all those kind of things. One of the things I've become more attuned to, talking to my colleagues who give a lot more immunotherapy, is that I always forget to ask a patient to take these things. Do you actively tell your patients, "Don't take it"? We should because all the data show that. I'm just curious what you guys are doing.

Rugo: We don't give antibiotics lightly anyway. I was really interested in those reports that suggested that patients might have more complications if they took antibiotics or that immunotherapy might not work as well.

There's a whole bunch of data out there, but it is all like, "Does coffee cause cancer?", which I saw another Medscape alert for. We need more data in this area, but I think we have to be cautious about this and use antibiotics judiciously.

For probiotics, it's an interesting question. I think there are enough data suggesting that they don't do very much, that it's reasonable to tell patients not to take them during treatment. I wish we had harder data on it. I can only just inform patients and let them know.

If somebody has an infection, I think we should treat them with antibiotics. If somebody is on steroids for a long time, I give them Pneumocystis pneumonia prophylaxis with Bactrim (trimethoprim/sulfamethoxazole) or a sulfa-type drug or atovaquone in sulfa-allergic patients. That is, of course, really important too, because we don't want to cause other issues.

I do think this high degree of suspicion is important. We've learned that if you are treating somebody who's profoundly hypothyroid, you do want to have a recent cortisol because you can really create many problems if you replace the thyroid and somebody is low on their ability to produced cortisol, which Zoe can speak to.

I had another patient who got immunotherapy. She was a very complicated patient who presented with dermatomyositis, acanthosis nigricans, new diabetes, and a triple-negative stage IIB cancer. She had a great response to neoadjuvant therapy. She had a little bit of residual disease, so she was going to have radiation before we discussed capecitabine. She continued on postoperative single-agent pembrolizumab in preparation for radiation therapy.

While being evaluated for radiation therapy, her mapping scan showed multiple lytic bone lesions and mediastinum adenopathy.

I ordered a PET-CT which showed lytic bone lesions and FDG-avid lymphadenopathy. We biopsied the bone and the pathology showed noncaseating granuloma, consistent with sarcoid.

I talked to rheumatology who recommended systemic immunosuppressive therapy, but she was asymptomatic, so I elected to follow her. On follow-up imaging, the lytic bone lesions and adenopathy had completely resolved. Quite fascinating. I did stop her pembrolizumab. Interestingly, her dermatomyositis has also largely resolved.

It just shows you that we can see unexpected and unusual toxicities with our novel agents, and particularly with immunotherapy. We have to be very suspicious for odd things, including nonendocrine toxicities.

Cardoso: There are some situations, particularly close to surgery, where there is prophylaxis with antibiotics. Do you discourage that or do you let surgeons do as per clinical practice?

Rugo: We don't. Rebecca, what do you?

Dent: No, we don't. I think with all of these things, you have to give prophylaxis for surgery. There's just no question. I think one dose and en route is absolutely fine. We don't.

Cardoso: Me, too. I just wanted to clarify that.

Rugo: That's a really good thing.

Cardoso: I don't want people to go to the other extreme.

Dent: No. I think the PPI question, though, is something really interesting because these are many drugs. I think we really underestimate it. In Singapore and in Canada, it's not over-the-counter, but in the US and many other parts of the world, you can get PPIs like you can get candy. I think that it is something that we underestimate but which can decrease effectiveness of certain drugs.

Rugo: It's an interesting question; we do use PPIs often because we know that gastritis contributes to nausea from our treatments. What are you doing now for those patients if you're not wanting to give a PPI?

Cardoso: You can give ranitidine or cimetidine.

Dent: Exactly. Famotidine. Many of them have what I call functional dyspepsia, where even with a PPI, they still have side effects because they have functional dyspepsia. I think Gaviscon (aluminum hydroxide–magnesium carbonate) or other oral agents are very helpful in combination with famotidine or ranitidine. I think they can help quite a bit.

Decisions Surrounding a Safe Return to Treatment

Rugo: That's an interesting question. One big question that comes up for us often, which I'd love your opinions on, is, when can you re-treat? We have patients who have had immune toxicities and recovered, but they are very high risk so you really want to give the checkpoint inhibitor. You always have to balance the potential benefits if somebody's not responding.

A related question: If you really want to give the checkpoint inhibitor, when do you hold for immunotoxicity? Do you hold for endocrine toxicities? If you do, which ones? When would you consider re-treatment?

Dent: It's interesting because I think we all have these general rules. With someone who had quite profound pneumonitis or colitis, I'm really inclined not to want to challenge. More recently, there were some data looking at percent success in rechallenging. I think it's considerably less for people that have pneumonitis or colitis. But you also have more challenges in terms of etiology that make it hard to know if it was the immunotherapy in the first place.

I would go through thyroid function. They're going to end up with thyroid dysfunction anyway, so I continue with the immunotherapy for thyroid dysfunction. As for adrenal insufficiency, thankfully, I have really had only one case.

The only other thing is I find that with some of the toxicities, like skin toxicity, sometimes people need a break. They're not severe, but patients are getting irritating and they've got a long duration of treatment. You've got those great success stories of many years.

It's the adjuvant patients that I'm finding a little bit more challenging. We know that in the adjuvant maintenance phase, patients do better, meaning they have less toxicity. I had a patient recently who just had nonspecific fatigue, which our endocrinologists can tell us about.

This nonspecific fatigue — was it due to surgery? Was it the recon? Was it 6 months of chemotherapy before their surgery? They're just not themselves despite exercise and all the healthy living, supportive things that they're doing.

I had this patient. She had gastritis and nonspecific GI stuff. I was convinced that she was adrenal insufficient. Her biochemistry was off. I just couldn't get her to feel better. I gave her a break and I put her on steroids. She was like a new woman.

I gave her a 4-week, fairly short-course taper, rechallenged her, and she got more rash, a little bit of fatigue, but she got on top of the exercise regimen. Dermatology is following her closely and giving her tons of topicals, and she seems to be managing.

I guess all of our patients are like this. The journey is so different for every patient. I think it's having us have to monitor that patient closely along with our specialists that can guide us as well.

Rugo: I had a patient who came in complaining of acute abdominal pain, about 2 weeks after completing neoadjuvant chemotherapy with a checkpoint inhibitor, and 2 weeks before planned surgery. Her initial evaluation was relatively benign and a CT of her abdomen was also unremarkable. We had her return to follow-up 2 days later.

At that time, her eosinophils were 10,000. With this remarkable finding, I thought we could go ahead and treat her with steroids and did not have to obtain a colonoscopy first. Indeed, with steroids she completely recovered, and her eosinophils returned to normal. We had a slight delay in time to surgery and a slow taper off of the steroids. We did not rechallenge her with immunotherapy.

Zoe, do you think it's safe to treat through hypothyroidism, hyperthyroidism, and adrenal insufficiency? Is there something different we should do with diabetes? We've seen two patients now with type 1 diabetes.

Quandt: For all the endocrine glands, somewhat unique to other immune-related adverse events, once it started, we think the gland is gone or on the way to being gone. We don't see any benefit in terms of the immune-related adverse events response from holding therapy. For adrenal insufficiency and thyroid disease, as long as the patient is stable enough, I say go ahead with it.

Really, the same for diabetes diagnoses. If someone's in diabetic ketoacidosis and they're admitted, you're going to have a treatment delay most likely because they're sick enough for that. If we're able to catch it early enough that we're managing as an outpatient, we can just go straight through without missing any doses.

I think it'll be interesting as we continue to collect cases to see if there are any situations where holding therapy might help with the remaining gland being preserved. At this point, we don't think there's any point to holding therapy.

The exciting thing, particularly with thyroid but with hypophysitis and diabetes as well, is that there's potentially this silver lining in that it's actually a marker of treatment response. Of course, you have some survival bias. Particularly with thyroid disease, it usually happens so quickly. In treatment, people haven't even had their restaging scans. We can say pretty clearly that it's associated with response across cancer types.

Cardoso: What is your experience with liver toxicity in terms of rechallenging? Let's say you have hepatitis grade 3; would you rechallenge? Hope? Rebecca?

Rugo: Initially we often see modest elevations in the AST or ALT, up to 100 or slightly higher. Then the issue a week or two later is that we see further elevation in the enzymes, up to 800. Of course we treat with steroids, but in those patients, we don't rechallenge.

These decisions can be really challenging. It does appear that we see more immune toxicity in patients treated in the early-stage setting than in patients treated for metastatic disease, probably because of the relative immunosuppression of metastatic disease or other issues that we don't understand as well. It doesn't appear to be PD-L1 expression alone. There's something else going on, because in the metastatic setting we're treating patients in the first-line setting.

I will say that, unless I didn't really know whether it was immune toxicity and the grade is 1-2, I don't rechallenge just because it's so dramatic. What do you do, Rebecca?

Dent: I'd have to agree with you. First, you have to figure out what the cause is. In the metastatic context, it's much less clear. In the early breast cancer context, it's much clearer. That's been my bigger challenge — just making sure.

Last week, I had a patient with normal liver function tests and then it was 500. She looked so clinically well. I was like, is this the immunotherapy? What's going on?

On further discussion, she was taking some multivitamins given by a friend. She was like, "Oh no, they're all natural." I said, "Stop them, get a scan, get your blood work." A week later, her liver function tests were trending down to 50% what they had been.

In general, if you have a sudden picture of transaminitis, where you don't have an etiology, we're unlikely to rechallenge. The GI and lung are two things that are a little bit more challenging and potentially life-threatening.

The other thing that's really curious is we really don't know how often you have to treat. I don't think you need to treat as long as the studies would suggest. There are great data by one of my colleagues, Chris Booth, who's actually looking at that. Hope, as you were saying, we are learning more about early vs late, when the immune system is more intact and you have less immune escape. That's potentially why you're seeing these sudden flares, right?

Cardoso: I wanted to highlight that when deciding to rechallenge or not, to have a look at the initial risk that made you go through with — I'm speaking about the early setting, so the initial risk for prescribing immunotherapy as well as the response to surgery. That may help you decide to rechallenge or not.

In the metastatic setting, that's a different situation because they will not be cured. I think, again, as we always do in oncology, the balance between quantity and quality of life in the metastatic setting is indispensable and don't forget that. In the early setting, despite being triple-negative, they are still potentially curable cancers. We certainly do not want the patient to die because of the treatment. This balance is fundamental.

Dent: Your point is really, really, really important, the differentiating factors there. Early, I rarely rechallenge except for in thyroid dysfunction, as you said, because these patients are potentially curable. We don't know how long we need to treat. It may even be just a few cycles that's actually of benefit. This is a really important point to anybody who's listening.

Rugo: We do treat through the diagnosis and treatment of adrenal insufficiency as well as thyroid disorders. I think the question of whether or not people need ongoing checkpoint inhibitor after surgery if they achieve a pathologic complete response is so incredibly important. Hopefully, in the next few years, we'll answer that question. In the meantime, there are many patients we're treating who might not really need the continued risk.

In patients with a pCR in particular, we should have a low threshold to stop in patients who have significant immune toxicity. Hopefully, we'll be able to figure this out. With combination immune therapies, whether you're giving them in clinical trials settings or whatever, these are patients who need to be monitored even more closely.

Optimal Management of Cardiac and Pulmonary Side Effects

Cardoso: In our last minutes, do you want to tackle some of the cardiac side effects?

Rugo: Or pulmonary?

Cardoso: Or pulmonary — the two that we have not mentioned yet.

Rugo: I haven't seen the cardiac toxicities, although we might have had one case in the neoadjuvant setting which was mild and resolved quickly.

I have seen pulmonary toxicity. It's a big surprise. The patient comes in coughing or saying, "I'm short of breath." The issue is that our patients are all a little bit short of breath on chemotherapy, even in the early-stage setting, because of associated anemia and fatigue, and we give them steroid premedications that can make their muscles weak.

You really have to have a very low threshold for obtaining a noncontrast CT scan because this toxicity can really explode to be very serious. It can take 6 months or longer to taper off steroids and impacts the patient's ability to go to surgery. We recently had a patient hospitalized for 6 weeks with pneumonitis in the early-stage setting. We don't even know which patients are at risk.

I have to say, the two patients in whom I have seen serious interstitial lung disease have been older and one had preexisting diabetes. Those are, by no means, defined risk factors validated in the trials. My colleague had one patient who was quite a bit younger, and for pulmonary toxicity, we don't rechallenge.

Rebecca, you've seen some cardiac toxicity.

Dent: Just one breast cancer patient. Because of it, we had a longer dialogue about it. Fortunately, compared with when we trained, we can get echocardiograms much more readily in emergency.

One of the things that I think is a real challenge if someone presents with shortness of breath is that it could be cardiac or it could be lung. Until proven otherwise, you get an echocardiogram and CT imaging and you move quickly.

The key thing in this particular situation is that you really can't underestimate how much the different organs interact, and it could even be both, to be honest. The key thing [in the patient I saw] was that people thought it was pulmonary but it was actually cardiac.

The Way Forward

We haven't talked about rheumatology today. Let's be honest — our colleagues who treat other tumors have really had to engage our rheumatology colleagues because there are many drugs that they use that are used in a patient who's having cardiac-related immune checkpoint inhibitor toxicity. This forced me to learn a little bit about some of the drugs that have been used. Again, don't forget about rheumatology.

I always find that dermatology, respirology, and endocrinology are the top three, but I would also say GI as well. We have really learned to refer even low-probability cases. They just get used to seeing what these patients look like. It's worked very nicely for us to focus in on one person within each department who sees our patients.

Rugo: Sometimes our patients do have immune toxicities that — thankfully, I've only had one ever — that require more than just steroids. In that case, we desperately need our colleagues to help us — all of our subspecialists.

Quandt: I think the cardiologist is probably one of the most important to have experience with immunotherapy patients because myocarditis is not common to begin with. We don't know how to treat it as well as the endocrine diseases, where we might have slightly different practices but we know these drugs really well. They're using really different treatments than you wouldn’t normally think about. Having someone with experience that you can call seems very critical.

Cardoso: I agree. I didn't see this in one of my patients, but I saw in a referral severe myocarditis after the first cycle. It can happen. We really need to be attentive and have our referral group of all the needed specialties.

I think we have covered most of the side effects, and we have emphasized throughout our discussion the importance of multidisciplinary discussion and care, and of not being afraid to refer, even if it's for a low-symptomatic patient. Because it's better to detect earlier, to treat earlier, and to manage properly. As we already discussed, we may be able to rechallenge — not all the time, but we may be able to rechallenge.

I thank everyone for joining us in this panel and I thank everyone for listening. Thank you.

Rugo: Thank you.

Quandt: Thank you.

Dent: Thank you.

Follow Medscape on Facebook, Twitter, Instagram, and YouTube


Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.