Early Immunotherapy Strategy Shows Strong Responses in Resectable Desmoplastic Melanoma

In this Pharmacy Times Q&A with Karen Knudsen, MD, PhD, the conversation explores promising research evaluating neoadjuvant pembrolizumab for patients with resectable desmoplastic melanoma. Knudsen discusses how the study’s approximately 70% complete response rate after just 3 doses of therapy highlights the potential for a paradigm shift toward earlier immunotherapy use. She also underscores the importance of care team coordination—including pharmacists—in maintaining treatment sequencing, preparing for immune-related toxicities, and guiding patients through the perioperative treatment window.

Pharmacy Times: Neoadjuvant immunotherapy appears to have produced dramatic tumor regression in desmoplastic melanoma. From your perspective, how could these findings reshape the standard treatment paradigm for this rare and historically difficult-to-treat melanoma subtype?

Karen Knudsen, PhD, MBA: Yeah, it’s such a great question. This is really an incredible advance—it's a small study, but still an incredible advance. If we think forward to how this might potentially shape the standard of care and shift the paradigm, a few things come to mind.

The first is: Is this a scenario where neoadjuvant checkpoint inhibitor therapy—PD-1 blockade—could become the default, the first move for resectable disease? This would shift systemic therapy to a position before surgery rather than reserving immunotherapy for adjuvant use. I think that’s an exciting question to ask, given that the pathologic response rate was 71%, which is incredible.

The second way this could shift the paradigm is that margin management could be absolutely transformed. This is a disease for which getting clean margins is historically very difficult. This approach holds the promise of reducing residual microscopic disease at the time of surgery, which would be a win for both the clinical team and the patient.

Most importantly for the patient, I think this means we have a real opportunity for treatment de-escalation. The intensity of treatment could be reduced for people who are actually strong responders. So, lots to love about the path forward here.

Pharmacy Times: For oncology care teams, what is most compelling about the depth of response observed with preoperative pembrolizumab, particularly in terms of surgical planning, long-term disease control, and patient quality of life?

Knudsen: I think that the most compelling component is what we just talked about: the 70% to 71% complete response after only 3 rounds, or 3 doses, of pembrolizumab. That’s the kind of response that we think of as being nonincremental and truly paradigm-shifting.

In this case, the promise is that we could achieve long-term disease control in this rare subtype. More data will follow to track those patients and see how that goes.

I also think about patient quality of life. These are patients who historically have had a challenging quality of life downstream of the diagnosis because of the historical need for repeated surgical intervention to resect the cancer as much as possible. Fewer repeat surgeries and less extensive resections lead not just to better outcomes but also to a reduced cosmetic burden on the patient and a better quality of life.

There’s major promise in those areas.

Pharmacy Times: Given the strong responses reported, how might pharmacists help identify appropriate candidates for neoadjuvant immunotherapy and educate patients about expectations, response timelines, and immune-related toxicities before surgery?

Knudsen: More data will come, but I would say that right now we can already start thinking about candidate identification—someone who has a resectable desmoplastic melanoma and is eligible for immunotherapy. Is this someone who would benefit from that new adjuvant–neoadjuvant strategy?

In terms of setting expectations, if the neoadjuvant strategy is chosen, it’s important to set expectations about the dosing schedule. Right now, it looks like 3 weeks for 3 doses, which equates, by my math, to about 9 weeks prior to surgery. So, understanding and helping the care teams and the patients understand what would happen and when is key.

It’s also important to ensure that someone is ready for any kind of toxicity or maintenance that needs to occur with regard to that neoadjuvant immuno-oncology strategy. In this study, there were very common events such as rash, fatigue, and diarrhea—nothing extraordinary that we wouldn’t expect, but still something that patients should be counseled about.

Pharmacy Times: As immunotherapy moves earlier in the treatment course, what role do you envision for oncology pharmacists in optimizing sequencing strategies and ensuring evidence-based integration into multidisciplinary care pathways?

Knudsen: I think that’s such an important and often overlooked question. I think owning that sequence integrity—ensuring that the neoadjuvant schedule is delivered on time—is critical. Based on this study, if we can get 71% of people to that response rate, we want to adhere to a strategy that we know is already potentially working.

Standardizing pathway-based decision support will come; that’s obvious. It will help lead the effort for immune toxicity readiness in the perioperative window. Those are some ways that pharmacists can assist in the sequencing and evidence-based integration.

Pharmacy Times: From a systems and research standpoint, how does the Parker Institute for Cancer Immunotherapy’s collaborative model help accelerate advances like this trial, especially in rare cancers that often lack large-scale clinical data?

Knudsen: I think this question hits the nail on the head. We have Parker Institutes across the country, and when it comes to rare disease, we are exquisitely poised to be able to share information and data about preclinical studies and clinical studies as they unfold because our networks are already fashioned in a way that has no encumbrances in terms of working together and sharing information that, of course, protects the patient’s identity.

We have an opportunity to really accelerate the clinic-to-biology feedback loop, if you will, based on the way that we are fashioned. The Parker Institute is laser-focused on game-changing immunotherapeutics, and this would be a perfect example of that. What’s notable is that this study, by my count, required 10 different investigator sites. Especially for rare diseases, it takes a tightly aligned network.

We see our role not just as resourcing these game-changing types of studies, but also as de-risking the science as it moves toward the time of clinical testing and making sure that all those data are reproducible so that when something gets to the phases of patient testing, we have every confidence in the science. This is a study that’s funded by SWOG, which is also a perfect example of that handoff to government funding that made this trial process possible.

It’s so important, and I think really important, to reinforce to the entire community the value of NIH [National Institutes of Health]-based clinical research, which we all know provides the most advanced form of cancer care for patients.

Pharmacy Times: Looking ahead, what additional evidence or follow-up data will be most important in determining whether neoadjuvant pembrolizumab becomes a new standard of care for desmoplastic melanoma?

Knudsen: As exciting as this study is, there are some things we’ll want to look at moving forward. Obviously, durability of the response with longer follow-up in these patients and others will be important. The second would be prospective confirmation in a larger, comparable data set.

We’ll also want to look at perioperative safety at scale and determine whether we can see these same types of results in a larger cohort of patients. Certainly, the need for this path forward is standard. It shouldn’t take away from the incredible results that were found in this study, from which a large number of patients benefited with a cancer that so frequently recurs.