Desmoplastic Melanoma and the Power of Neoadjuvant Immunotherapy

For patients diagnosed with desmoplastic melanoma, the road to recovery has traditionally been paved with aggressive interventions. This rare and invasive form of skin cancer often necessitates surgeries that can leave behind scars. However, a clinical trial from the UCLA Health Jonsson Comprehensive Cancer Center, a Parker Institute for Cancer Immunotherapy (PICI) Center, is signaling a major shift in the treatment paradigm.

The study explores the neoadjuvant approach: administering the immunotherapy drug Keytruda (pembrolizumab) before a surgeon ever picks up a scalpel. Researchers observed dramatic tumor shrinkage and, in many instances, the total elimination of detectable disease prior to surgery.

CURE sat down for an interview with Karen Knudsen, CEO of the Parker Institute for Cancer Immunotherapy to discuss how this strategy could redefine the standard of care for patients with desmoplastic melanoma.

For many years, the standard treatment for desmoplastic melanoma has involved extensive, often life-altering surgery. Could you explain how giving immunotherapy before surgery fundamentally changes the patient’s experience and surgical outcome?

The checkpoint inhibitors, which is the kind of immunotherapy that was used here, have a really unique strategy to train your immune system to see a cancer it normally is blocked from seeing. Cancers are very good at cloaking themselves, if you will, from your own immune system. The way that checkpoint inhibitors work, in effect, is to lower the cloak so your immune system has a better ability to see something that is not you — it started off as you and those cells became cancerous and started to look different; your immune system would normally have eliminated them, had there not been for this cloaking mechanism.

It turns out that desmoplastic melanomas have these features where your immune cells can identify and clear them in the presence of a checkpoint inhibitor. There were early studies showing that this would work. The way that this study worked, I think, is just brilliant in its design. It's let's take the thing that we know works for these patients — surgery, often multiple, but let's start there. Let's start with surgery, and then give them this checkpoint inhibitor to test the idea that when you've gotten rid of the bulk of the tumor, that anything that's remaining, that's residual, that could still be there, could be eliminated more easily by your immune system, because it's fewer cells really for them to have to attack. That's the way this worked.

The way that this trial was run afforded patients a better quality of life by having surgery and immunotherapy in a way that prevented their recurrence. The data were actually really quite stunning to show that we could prevent these cancers from becoming meaningful.

Transcript has been edited for clarity and conciseness.

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