Experience Managing irAEs Vital for Both Oncologists and Specialists

James W. Smithy, MD, MHS

Assistant Attending Physician

Memorial Sloan Kettering Cancer Center

New York, NY

DISCUSSION QUESTIONS

• Discuss your comfort level in managing immune-related adverse events (irAEs) in the setting of metastatic melanoma.
• How has this changed over time?

James W. Smithy, MD, MHS: Thinking back 5 or 10 years when immunotherapy was newer, what was it like managing irAEs? How do you think about treating those now? How does that inform your choice of therapy?

Chandar Bhimani, MD: We are very comfortable with immune-mediated toxicity. Seven or 8 years ago, when we started, it was a learning curve. When it happens, it's worrisome and you have to deal with it. You have to hold the treatment, start the steroids, and try to see what's your next step will be. But I've been very comfortable lately, since its use has been in multiple tumor types, so the experience is growing. We are seeing more immune-mediated AEs [because] the incidence going up as its use is going up in different tumor types. The comfort level is better, but toxicity does happen, and when it happens, it's quite concerning.

Sherine Thomas, MD: As far as I'm concerned, the spectrum matters. Everybody has seen and managed hypothyroidism and a few thyroiditis cases. I'm sure that's not a problem for almost anybody on this panel. But what is more serious is hypophysitis. I've had a couple of patients where I was unsure if it was immune mediated but there was a bone marrow shutdown situation with severe pancytopenias that lasted an unusually long time, almost 4 weeks. They were in a hospital for a couple of weeks. So those things do become a little bit tricky. Hypophysitis diagnosis, getting the [dexamethasone suppression] test and things like that, ends up requiring other specialties involved. Those become a little dicey, but it depends on what the toxicity is that we're talking about.

Venu Konala, MD: The challenges we have in the community setting is getting to a specialist for these things. I had couple of patients where I sent the patient for autoimmune-related pancreatitis 6 months after discontinuing nivolumab. The gastroenterologist put them on pancrelipase (Creon) and sent them back to me, so I have to treat them with steroids, and if they're not working, put them on mycophenolate.

That awareness is not there with every specialty. That's something hard, because [I had a patient] who stopped nivolumab [Opdivo], and she developed joint pains all over her body. I sent her to rheumatology, and they called me and said that if you think it's autoimmune related, we'll give tocilizumab [Actemra], but they hadn’t assessed her and hadn’t made the decision. They left it up to me. You can develop autoimmune-related AEs even up to a year after you discontinue it.… They're not making those decisions because they're not comfortable, or they haven't seen too many patients with those conditions.

Smithy: Yes, I think that's probably a unique challenge. In a large academic center, we're spoiled by having a lot of specialists who do this. Seeing how their management strategies have changed over the last few years is interesting too, because I think we are moving beyond steroids for a lot of these and thinking about alternate immune-suppressant agents that don't have as much effect on immunotherapy's anti-cancer response is an important thing, too.

There were some data that came out [in 2024] in melanoma that [giving] people high-dose steroids does seem to impede effectiveness of [immunotherapy] against melanoma.¹ Trying to walk that balance and seeing what alternative agents you can try for refractory cases, like second- or third-line colitis treatment is important. As much as you can, try and develop relationships, but it sounds hard in other places.

_{DISCLOSURE: The participants had no known relevant disclosures.}

_Reference:

_{1. Verheijden RJ, Burgers FH, Janssen JC, et al. Corticosteroids and other immunosuppressants for immune-related adverse events and checkpoint inhibitor effectiveness in melanoma. Eur J Cancer. 2024;207:114172. doi:10.1016/j.ejca.2024.114172}