The immune checkpoint inhibitor pembrolizumab achieved high response rates in patients with unresectable metastatic desmoplastic melanoma, a rare invasive tumor type, according to the results of the phase II SWOG S1512 trial presented at the 2023 American Association for Cancer Research (AACR) Annual Meeting.¹ The overall response rate in this small study was 89%, with a complete response rate of 30%. The safety profile of pembrolizumab was consistent with previous reports of single-agent anti–PD-1 therapies in metastatic melanoma.

“The response rates were dramatic,” noted lead author Kari Kendra, MD, PhD, of The Ohio State University Comprehensive Cancer Center in Columbus. “Patients with desmoplastic melanoma are exceptional responders to single-agent PD-1 blockade with pembrolizumab. Based on these data, single-agent anti–PD-1 immunotherapy should be considered the first-line treatment of choice for most patients with unresectable desmoplastic melanoma.”

Kari Kendra, MD, PhD

Desmoplastic melanoma is rare, accounting for about 4% of all cutaneous melanomas. It is amelanotic (lacking the dark pigment more typical of melanoma), usually found in highly sun-exposed areas, and is more common in the elderly and among men.

Previous studies have shown that desmoplastic melanoma is characterized by high levels of tumor mutational burden, which could theoretically make it sensitive to checkpoint inhibitors. Pembrolizumab is already approved for first-line treatment of unresectable melanoma. The current study is the first prospective trial of pembrolizumab in patients with the desmoplastic subtype.

Study Details

The prospective study enrolled patients with histologically and genetically confirmed desmoplastic melanoma who had not received prior treatment. Cohort A evaluated neoadjuvant pembrolizumab in patients with resectable disease; Cohort B evaluated pembrolizumab in patients with unresectable metastatic melanoma. Previously reported results of Cohort A showed a pathologic complete response in 58% of patients. Dr. Kendra reported the results of Cohort B at the AACR meeting.

In Cohort B (n = 27), the median age of patients was 75, and 93% were men. The primary site of disease was the head or neck in 63%, an extremity in 19%, and the torso in 19%. Patients received pembrolizumab at 200 mg intravenously every 3 weeks for 2 years. The median number of cycles of pembrolizumab was 15, which added up to about 45 weeks of therapy.

Responses to therapy were rapid, with some occurring in most patients within 9 weeks, including complete responses. Nine patients (33%) achieved a complete response to the single-agent pembrolizumab (P < .001), meeting the study’s primary endpoint of a complete response of at least 20%. An additional 15 patients had partial responses, for an overall response rate of 89%.

For the secondary endpoints, the 2-year progression-free survival rate was 74%, and the 2-year overall survival rate was 89%. Eight patients had died at the time of the analysis, six as the result of other comorbidities, one from disease progression in the central nervous system, and one from an unknown cause.

“Keep in mind our patient population had a median age of 75, going up to 90, and all had multiple comorbidities,” Dr. Kendra said.

Adverse events were similar to those seen previously with PD-1 blockade in melanoma. Adverse events of any grade were reported in 93%; the rates of grades 1, 2, 3, and 4 adverse events were 11%, 44%, 30%, and 7%, respectively. The most common events were fatigue, diarrhea, maculopapular rash, pruritus, anemia, arthralgia, and decreased lymphocyte count.

Two grade 4 adverse events were reported: increased lipase in one patient and lung infection and sepsis in a second patient. 

DISCLOSURE: The study was funded in part by Merck Sharp & Dohme. Dr. ­Kendra has served as an advisor to Pfizer, OncoSec, Regeneron, Genentech, Novartis, Natera, Replimune, Sanofi, BMS, Merck, Iovance Biotherapeutics, Genzyme, Nektar, Castle Biosciences, Instil Bio, and the National Comprehensive Cancer Network (via Pfizer). She is on the scientific advisory board for Advaxis, Appia, Apricity, Arcus, Compugen, Highlight, ImaginAb, ImmPact, ImmuneSensor, Inspirna, Isoplexis, Kite-Gilead, Lutris, MapKure, Merus, PACT, and Pluto.

REFERENCE

1. Kendra K, Bellasea S Eroglu Z, et al: S1512: High response rate with single agent anti-PD-1 in patients with metastatic desmoplastic melanoma. 2023 AACR Annual Meeting. Abstract CT009. Presented April 16, 2023.