dMMR Recurrent EC: Practical Advice on Adverse Event Management


Key opinion leaders in the field of endometrial carcinoma provide advice on adverse event management, focusing on immune checkpoint inhibitor therapy.


Robert L. Coleman, MD, FACOG, FACS:One of the things that we will talk about in this patient is that she ultimately ended up getting radiation, mostly for the symptomatic issue around the urethra and distal vagina. She then ended up getting pembrolizumab [Keytruda] at the 2 to 3 week [mark], standard dosing at 200 mg [milligrams] every 2 to 3 weeks. Interestingly, since we already preempted all this, she ended up getting a partial response by imaging at 4 months. But in cycle 9, she reported fatigue, weakness and 10-pound weight gain. And just as you mentioned, Krish, she ended up getting kind of the panel. And you can see she was identified with an unusual type of hypothyroidism. She has a low TSH [thyroid stimulating hormone] with low T4 [thyroxine], so her thyroxine was replaced and ultimately she did well.

Krishnansu S. Tewari, MD: That is a strange hypothyroidism.

Robert L. Coleman, MD, FACOG, FACS:Yeah, and I've seen this 1 other time. There is a condition that is associated with the immune checkpoint inhibitors that causes the reduction of both of those. You don't get the reflexive TSH increase. So has this little bit of more of a central effect on the hypothyroidism and hypothalamus. So, I think we've discussed this pretty well… about how we approach symptomatology with these patients, and Kimberly, your discussion is really well taken. How do you deal with rash? You mentioned [skin rash] and it perked my ears because I know I haven't been so good with it, but how do you deal with rash?

Kimberly Halla, MSN, FNP-C: Skin, right? Skin is the bane of my existence in this one, right?

Robert L. Coleman, MD, FACOG, FACS:Exactly.

Kimberly Halla, MSN, FNP-C: Being from Arizona, skin can be different just from the dryness and different things that way. We start easy. Don't forget the basics when you're talking about skin and rash, right? So, if it's just something irritable, some topical corticosteroid will work, but never fail to have a good dermatologist on hand as well, right? So, knowing who your colleagues are in the community and knowing where your patients can get into and be seen rather quickly has really helped. I'm no longer getting pictures over their electronic medical record about skin and rashes, because it's just one of those things that I'm not an expert in.

Robert L. Coleman, MD, FACOG, FACS:Well, and in Phoenix, or in Arizona in general, that's a lot of sun exposure. How do you keep them out of the sun? They've got to walk around and be completely covered? Hats and everything.

Kimberly Halla, MSN, FNP-C: You know what? You try, but it's not a very good suggestion that is well taken.

Robert L. Coleman, MD, FACOG, FACS: Yeah. Especially here in Houston, not only do we have nail salons, we have tanning booths with them. So, it's just great. You get all this exposure to the sun, like we need it in Houston. So, Krish, I think a lot of people don't have a lot of experience with the immune checkpoint inhibitors. What resources do you use to deal with maybe that toxicity that you're not so familiar with in terms of mitigating strategies? What do you do with their dose? How long do you hold it? Do you give steroids? What’s your general approach? And then where do you go to find good resources that people could maybe look up?

Krishnansu S. Tewari, MD: Yeah, I’m very liberal with steroid use in these patients. And I think that helps attenuate the reaction. If patients are doing well, I will hold it. I'll rechallenge them again. If they get another rash, I may even discontinue it if the rash bothers them. I have 3 Kimberlys at my practice and they are invaluable.

Robert L. Coleman, MD, FACOG, FACS: You're so lucky.

Kimberly Halla, MSN, FNP-C: What a lucky guy you are.

Krishnansu S. Tewari, MD: I have 3 wonderful nurse practitioners and they are invaluable. But I also use consultants. With dermatology, we have a good dermatologist, but oftentimes we'll send the patient to them, and the dermatologist will send us a note, "It's due to the checkpoint."

Robert L. Coleman, MD, FACOG, FACS:Thanks. That'll be a level 4. Yeah, exactly.

Krishnansu S. Tewari, MD: But the rare stuff, I think it's really important to work with your endocrinologist, closely. I have a lady with hypothyroidism, and not only is she having T4 supplementation, but she's also getting T3 [triiodothyronine] supplementation, which is something I would [have] never thought of.

Robert L. Coleman, MD, FACOG, FACS:Wow.

Krishnansu S. Tewari, MD: You know, there's commercially available T3 supplements to help with some of these more unusual or immune mediated hypothyroidisms. So having an endocrinologist is key. I've had some bizarre experiences where patients, in timing with their pembrolizumab infusion, they develop bilateral lower extremity weakness, which is not a recognized side effect. I thought, “This must be neuropathy from chemotherapy,” but the timing can't be coincidental. And so I've also worked with neurologists just to see if there's anything they can add. But I'm very liberal with steroids. I'm good to my nurse practitioners, so they help me.

Kimberly Halla, MSN, FNP-C: Smart man.

Krishnansu S. Tewari, MD: I also had a lady with adrenal insufficiency, kind of like you did, and so, working with the endocrinologist has been really helpful.

Robert L. Coleman, MD, FACOG, FACS:Yeah. I'll point out to people that are interested. The GCO [Global Cancer Observatory] published a pretty big monograph about every adverse event and how you manage it. So, I would refer you to that. It's been recently updated, brought in additional nuances to management and it's actually really helpful. I keep a copy on my iPad so I can carry around with me and look up stuff if it's something unusual. So great discussion here.

Transcript edited for clarity.

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