Checkpoint inhibitor

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Hello, and welcome to this podcast, where we will be providing perspectives on 10 years of immune checkpoint inhibitors in Merkel cell carcinoma.

My name is Paul Niem, and I'm a professor at the Department of Dermatology at the University of Washington and the Fred Hutch Cancer Center in Seattle.

Dr. D'Angelo, can you say hello, please?

And it's great to be talking on that topic with all of you today.

Excellent.

In this podcast, we'll be discussing several questions related to the use of immune checkpoint inhibitors, or ICIs, in the treatment of Merkel cell carcinoma, or MCC.

These will address findings from key studies in advanced Merkel cell carcinoma and consider areas of specific interest, including when to stop ICI treatment.

Looked at about almost 200 patients with gastric cancer, also relatively limited enrollment in clinical trials.

If we look at the immune checkpoint inhibitors in this space, it's a fairly heterogeneous population.

So you have NEVO.

You have some IV NEVO, and I know we're going to address some data with that in the neoadjuvant setting later, but also some PIMBRO and DERVA utilization.

Most of the people are positive, greater than one.

So about 80% of gastric and esophageal cancers will be CPS positive at a score of one or higher.

And the totality of the data, the FDA reviewed all this, And rather than have multiple cut points for multiple trials, which is how the trials were done, they basically said anyone who's positive seems to have a chance of benefiting, and the population who have a PD-L1 score of less than one, the truly negative people, they're probably not getting any benefit, and the juice is just not worth the squeeze for adding any of the checkpoint inhibitors.

So the FDA label is essentially PD-L1 greater than one.

But these last few years, this has been a success story in some way because we've seen so much effort and research into this rare disease space, which is encouraging.

We mentioned this at the top, but there are immune checkpoint inhibitors that have at least been trialed for this T cell exhaustion to see if we can boost the immune system.

And then more recently with your work around allogeneic specific T cells to help clear the infection.

what have you taken away from those updates

the biggest takeaway is that these two approaches checkpoint inhibitors and virus-specific t-cells have really transformed the way that we think about pml so for decades our only option was really to try to reverse the underlying immune suppressive condition and just hope that the immune system caught up in time and now we have these two active strategies to try to speed this process up.

Importantly, both these strategies have validated the same core hypothesis that even without a direct antiviral agent, we can improve PML outcomes by restoring effective antiviral immunity.

And that said, each of these approaches has real limitations.

So first of all, they don't work in all patients.

We will move on to our next paper.

This is Immune Checkpoint Inhibitors for Advanced Periocular Orbital Squamous Cell Carcinoma of Cutaneous Origin, Durable Responses in a Retrospective Cohort.

And we have our expert ocular oncologist, Dr. Kelsey Roloff, to discuss this paper with us.

This is from the group out of Mass Eye and Ear with Ami Azad as the primary author and Natalie Wolko as the senior author.

So if we have radiographic evidence of pneumonitis, the safest thing is to stop and treat, treat the pneumonitis, and then consider resuming therapy or no.

So I think with immune checkpoint inhibitors, when we see pneumonitis, we're a little bit more relaxed and we continue to treat with immune checkpoint and we treat the pneumonitis.

Of course, as long as it's grade one, grade two.

But I think with the ADCs, it's probably not safe to do.