Neoadjuvant Immunotherapy Shows High Response Rates in Desmoplastic Melanoma

Neoadjuvant pembrolizumab induced pathologic complete response in 71% of patients with resectable desmoplastic melanoma, according to results from the phase 2 SWOG S1512 trial. The multicenter, two-cohort study enrolled patients between July 2017 and May 2021 and demonstrated that three cycles of neoadjuvant pembrolizumab over 9 weeks, followed by surgical excision, achieved a pathologic complete response rate of 71% (95% CI, 51%-87%), far exceeding the study's primary endpoint goal of 20%.

The trial included 28 patients with resectable disease (median age, 75 years; 75% men; 96% white), with 19 patients (68%) having primary disease on the head and neck. At 3 years, 87% (95% CI, 65%-96%) of patients who underwent resection remained alive and 74% (95% CI, 51%-87%) remained relapse free. Median overall survival and relapse-free survival had not been reached at a median follow-up of 42 months. Long-term data for both resectable and unresectable cohorts reported only two melanoma-related deaths among 55 patients.

The approach may help some patients avoid extensive and potentially disfiguring surgeries. Desmoplastic melanoma, which accounts for about 4% of all melanomas, tends to infiltrate deeply into the skin and go through the nerves. Due to frequent perineural invasion, lesions often extend beyond what is visible clinically or on imaging, requiring large excisions and follow-up surgeries to remove residual disease.

Twenty-two patients (79%) reported any-grade treatment-related adverse events, the most common of which included fatigue (43%), maculopapular rash (21%) and diarrhea (14%). Two patients (7%) experienced grade 3 treatment-related adverse events, with one case each of mucositis and immune-mediated colitis.

In separate research on advanced melanoma treatment, a lower dose of ipilimumab combined with nivolumab showed improved outcomes compared to standard dosing. The study followed nearly 400 people with advanced, inoperable malignant melanoma and found that patients receiving the lower dose of ipilimumab responded better to treatment, with 49 percent experiencing a measurable response compared with 37 percent among those who received the traditional dose.

Progression-free survival reached a median of nine months in the lower-dose group compared with three months for the standard dose. Overall survival also differed substantially, with patients in the reduced-dose group living a median of 42 months compared with 14 months in the traditional-dose group. Severe side effects occurred in 31 percent of patients given the lower dose, while 51 percent of those receiving the conventional regimen experienced serious complications.

The established and approved treatment for advanced melanoma combines nivolumab and ipilimumab at specific standard doses. However, because this regimen is often linked to significant side effects, Swedish doctors have increasingly adopted a strategy that reduces the amount of ipilimumab, which is the costliest component of the combination therapy and is also responsible for many of its most severe adverse reactions. Although some baseline differences existed between the two patient groups, the improved outcomes linked to the lower dose remained even after researchers accounted for factors such as age and tumor stage.