Immunotherapy is a resounding success for the treatment of many cancer types, including those malignancies which previously had no reliable therapy to offer patients such as cutaneous (skin) melanoma. This success was the reason that an international study conducted an investigation on whether combination ipilimumab (Yervoy) and nivolumab (Opdivo) could offer a survival benefit to patients with acral melanoma. Unfortunately, the treatment had little impact.
Acral melanoma is a rare melanoma subtype that primarily occurs on the palms of the hands, soles of the feet, or the nailbeds—the non-hair-bearing surfaces of the body. Acral is biologically distinct from cutaneous melanoma, is thought to develop after significant injury or trauma to an area, and has a worse prognosis in comparison. Current guidelines do not always distinguish acral from cutaneous melanoma, which is problematic.
Since immunotherapy is therapeutic for many types of cancer, an international cohort of investigators conducted a retrospective analysis on acral melanoma. The current study examined the efficacy of combination immunotherapy with ipilimumab and nivolumab in 109 patients with Stage III (25.7%) and Stage IV (74.3%) disease.
Despite success with cutaneous melanoma, only 18.4% of patients (n=20/109) with acral melanoma responded to therapy, including 8.3% (n=9) with complete responses and 10.1% (n=11) with partial responses. Twenty-two patients (20.2%) had stable disease and the disease control rate was 38.5%.
In comparison, the CheckMate-067 study investigating PD-1/CTLA-4 inhibition in patients with cutaneous melanoma showed an overall response rate of 57.6%. This study’s overall response rate for patients with acral melanoma treated with PD-1/CTLA-4 inhibition was 18.3%.
The current study contained 73.4% (80/109) of patients who progressed with acral melanoma despite the combination of ipilimumab and nivolumab. Among the patients, 87.2% (n=95) experienced low-grade toxicities related to treatment, which was most commonly fatigue (30.3%), rash (22.9%), and pruritus (14.7%). Among the higher-grade toxicities, 40.4% (n=44) experienced grade 3-4 effects, which included colitis and hepatitis.
Overall, the results of the retrospective analysis’s results for acral melanoma were disappointing, given that ipilimumab plus nivolumab yields very good outcomes for advanced cutaneous melanoma. Recent clinical trial results demonstrated that 43% of patients with advanced cutaneous melanoma survived 10 years after their diagnosis when treated with ipilimumab plus nivolumab.
Although ipilimumab and nivolumab are approved in combination for at least seven other types of cancer, an insufficient number of patients with acral melanoma were included in previous clinical trials to definitively understand whether efficacy existed.
Several reasons are attributed to the reduced number of acral patients in trials, including the scarcity of patients with acral melanoma, the availability of the cohort to enroll in a trial, and the exclusion of acral in trials specific to cutaneous melanoma. Nevertheless, the lack of clinical trials for patients with acral melanoma left a gap in understanding whether immunotherapy might be therapeutic for acral, too.
Ongoing clinical trials for acral melanoma examine other potential efficacy options, such as triplet combinations with doublet PD-1 inhibitors, temozolomide, or VEGF inhibitors. The study authors cite the lack of immune recognition and lack of tumor-infiltrating lymphocytes within acral melanoma as major reasons for the failure of PD-1/CTLA-4 inhibitors.
Reference: This summary is based on the publication “Combined PD-1 and CTLA-4 Blockade in an International Cohort of Patients with Acral Lentiginous Melanoma” in The British Journal of Dermatology by Erin McGillivray, Karam Ashouri, Eftychia Chatziioannou, et al. on October 23, 2024. DOI: 10.1093/bjd/ljae401
