Hensin Tsao, MD, PhD: TIL Therapy and Neoadjuvant Treatment for Pigmented Lesions

It’s an exciting time for dermatology providers caring for patients with melanoma, according to Hensin Tsao, MD, PhD, clinical director of the Melanoma & Pigmented Lesion Center at Massachusetts General Hospital. His presentation at Maui Derm NP+PA Fall 2024, held September 15-18, 2024, in Nashville, Tennessee, focused on TIL therapy for patients who fail to respond to first-line treatments, the rise in popularity for neoadjuvant treatment, atypical clinical presentation of melanoma, and personalized cancer vaccines.

This transcript has been edited for clarity.

Dermatology Times: Tell us about your session on pigmented lesions presented at Maui Derm NP+PA Fall, and why it’s important to provide this education to an audience of advanced practice providers?

Hensin Tsao, MD, PhD: This session embodies a lot of components of melanoma. We have Dr. Ashfaq Marghoob and Dr. Elena Hawryluk, who are going to join me and talk about the management of melanoma from different perspectives, such as the pediatric dermatologist and pediatric pigmented lesions. I, myself, will tackle the task of melanoma itself, sort of from A to Z. I'm going to look at biopsies. I'm going to look at surgery. And, perhaps the most exciting part of melanoma medicine right now, which is all the treatments that are coming down the pipeline in terms of tackling metastatic melanoma. It's an incredibly important topic. It's a topic that's evolving very rapidly and I think, as dermatology providers, we are obligated to our patients in some way to keep up with what's going on in the field.

DT: Can you discuss any recent advancements in the management of pigmented lesions, including how these newer approaches compare to traditional treatment modalities?

HT: For dermatologists specifically, and then I can talk about broadly how it affects the global melanoma population, but for dermatologists specifically, I think there are a couple areas that are emerging that are incredibly exciting and again, rapidly moving. For instance, there have been recent trials looking at high-risk primaries, those melanomas that are really thick, really large. You've seen them. Everyone has seen them. Now, there's some evidence that even in the absence of having any melanoma in the lymph nodes after a sentinel biopsy, and having no melanoma on any of the radiological workup, a high-risk melanoma would benefit from treatment with systemic agents. So if you had a patient who came in with a 4-, 5-, 6-millimeter melanoma, you do a central biopsy. It's negative. After surgical removal of that melanoma, that patient should be referred to a medical oncologist for consideration, say, for immune checkpoint inhibition. So that's something that has really emerged in the past couple years.

Traditionally, I think for dermatologists and providers such as dermatologic PAs and NPs, generally removing the melanoma and sort of watching the patient has been our call, but now there's really good evidence, again, that some of those patients would benefit from adjuvant treatment.

The other area that's evolving very quickly, something called neoadjuvant treatment. Traditionally, we do surgery on the primary melanoma, and then if there's no evidence of disease anywhere else, then we give the treatment. Now, a patient comes in and they've got a large mass in the left groin. They've got a large mass in the right axilla, and you find out that that's, in fact, metastatic melanoma. Before surgery is done to remove that mass, you can pre-treat the patient with some immune checkpoint inhibitors, and it looks like this early treatment, even before surgery, confers a better survival advantage than removing the tumor first and then treating afterwards. So neoadjuvant melanoma treatment is now becoming really a fantastic mainstay of melanoma management.

DT: Can you describe the current therapeutic toolbox for pigmented lesions? What are some areas of unmet need?

HT: There's been a lot of development in the immune treatments for melanoma. I think everyone's heard about their traditional ones — ipilimumab, pembrolizumab, nivolumab — but more recently, for really for advanced-stage melanoma, relatlimab, which attacks this protein called LAG-3, is really coming into play to try to improve survival.

Now for patients who fail to respond to these first-line treatments, taking the lymphocytes, the cytolytic lymphocytes, the real cells that are attacking the melanomas out of a patient's tumor, growing them up in a tissue culture situation, and infusing them back to the patient is something that has now been approved by the FDA. This is called TIL therapy. And I think this is really exciting for patients who have in some way failed that first-line therapy. And unfortunately, those patients are really tough to treat, but with now sort of second-line treatments coming into being, I'm really hopeful that those patients, again, who did not respond initially, will have some hope now, sort of down the horizon, really looking at the future with excitement.

With personalized cancer vaccines, now we can take a small piece of your tumor, sequence all the mutations that occur in that tumor, and create a personalized cancer vaccine for you to be used in order to try to mitigate the melanoma tumor. So it is, in some ways, the ultimate use of the Human Genome Project, and to use the specific mutations we see in your melanoma really back against the melanoma that you have.

DT: What are some of the other pearls to highlight from this talk?

HT: I think 1 of the things now — I’ve been practicing a long time, much older than you think — is that melanomas don't look like the textbooks. I think there's been this phenomenon in which us teachers, clinicians, or any clinician involved, wanted to really capture images of melanoma. [We] traditionally take pictures of things that look like classic melanomas, you know, those large ABCD sort of lesions. But I think as you go back now through the records and look at what actual melanomas look like, often they are not the classic picture that you tend to see. Sometimes they're pink, sometimes they're red, sometimes they hide in or look like seborrheic keratosis. I think 1 of our lessons going forward is to fully understand the full spectrum of what melanomas look like. It's only then can we sort of start teaching our colleagues on the breadth of what melanomas can resemble and, in some ways, the threat. I think that's one area that we are beginning to sort of learn more about.

Now there are newer and newer guidelines that are coming out looking at the possible utility of technologies, molecular technologies, staining technologies, imaging technologies, that can be used as a dermatology aid to try to help diagnose or detect melanoma. I'm incredibly excited about those opportunities. I think the real key is finding out the exact patient population, the exact situation where you might want to deploy these technologies. From a dermatologist and from the skin perspective, I think certainly molecular imaging technologies will continue to be in our research program and will continue to be, certainly an aspirational goal to incorporate into our clinical practice. But certainly, I think we also want to be reminded that the disease itself is a lot trickier sometimes that we think.

I think it's an incredibly exciting time for melanoma, probably more exciting than I've seen it in the last 4 decades. But because there're so many advancements, we really have to keep track of these things as they come out. The [National Comprehensive Cancer Network] does a great job. The AAD’s putting together guidelines. It’s 1 of the few areas in dermatology where there's really great evidence and cross-participation from different specialties to really focus on a single patient. I've always enjoyed taking care of melanoma patients … No matter what you're going to see them in your clinic, and I hope you keep up with all the advancements so you can really fully take care of your patients to the best possible extent.

Reference:

Tsao H, Hawryluk E, Marghoob A. Pigmented lesion clinic – new interactive format. Presented at: Maui Derm NP+PA Fall; September 15-18, 2024; Nashville, Tennessee.