Response to immune checkpoint inhibitors in acral melanoma: A nationwide cohort study

• Published in: European journal of cancer (1990) Vol. 167; pp. 70 - 80
• Main Authors: van Not, Olivier J., de Meza, Melissa M., van den Eertwegh, Alfons J.M., Haanen, John B., Blank, Christian U., Aarts, Maureen J.B., van den Berkmortel, Franchette W.P.J., van Breeschoten, Jesper, de Groot, Jan-Willem B., Hospers, Geke A.P., Ismail, Rawa K., Kapiteijn, Ellen, Piersma, Djura, van Rijn, Roos S., Stevense-den Boer, Marion A.M., van der Veldt, Astrid A.M., Vreugdenhil, Gerard, Bonenkamp, Han J., Boers-Sonderen, Marye J., Blokx, Willeke A.M., Wouters, Michel W.J.M., Suijkerbuijk, Karijn P.M.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.05.2022; Elsevier Science Ltd
• Subjects: Apoptosis; Cell death; Cohort analysis; Cohort Studies; Humans; Immune checkpoint; Immune checkpoint inhibitors; Immune Checkpoint Inhibitors - therapeutic use; Immunotherapy; Inhibitors; Ipilimumab - therapeutic use; Medical prognosis; Melanoma; Melanoma - mortality; Melanoma, Cutaneous Malignant; Nivolumab - adverse effects; Patients; PD-1 protein; Prospective Studies; Response; Response rates; Skin Neoplasms - drug therapy; Skin Neoplasms - immunology; Statistical models; Survival; Response; Immune checkpoint inhibitors; Survival; Immunotherapy; Melanoma
• ISSN: 0959-8049; 1879-0852
• DOI: 10.1016/j.ejca.2022.02.026

Recent reports suggest the limited efficacy of immune checkpoints inhibitors in advanced acral melanoma (AM). This study aims to investigate the clinical outcomes of immune checkpoint inhibitors in patients with stage III and IV AM and compare them to cutaneous melanoma (CM). We included patients with advanced AM and CM treated with first-line anti-programmed cell death (PD)-1 monotherapy or ipilimumab-nivolumab registered in the prospective nationwide Dutch Melanoma Treatment Registry. Objective response rates, progression-free survival (PFS) and overall survival (OS) were calculated. A Cox proportional hazard model was used to assess the prognostic factors with PFS and OS. In total, 2058 patients (88 AM and 1970 CM) with advanced melanoma were included. First-line objective response rates were 34% for AM versus 54% for CM in the advanced anti-PD-1 cohort and 33% for AM versus 53% for CM in the advanced ipilimumab-nivolumab cohort. The Median PFS was significantly shorter for anti-PD-1 treated AM patients (3.1 months; 95%CI: 2.8–5.6) than patients with CM (10.1 months; 95%CI: 8.5–12.2) (P < 0.001). In patients with advanced melanoma, AM was significantly associated with a higher risk of progression (HRadj 1.63; 95%CI: 1.26–2.11; P < 0.001) and death (HRadj 1.54; 95%CI: 1.15–2.06; P = 0.004) than CM. This study shows lower effectiveness of anti-PD -1 monotherapy and ipilimumab-nivolumab in AM, with lower response rates, PFS and OS than CM. This group of patients should be prioritised in the development of alternative treatment strategies. •Largest Western advanced acral melanoma (AM) and cutaneous melanoma (CM) cohort.•Response rates for anti-PD-1 and ipilimumab-nivolumab treated AM inferior to CM.•Lower progression-free and overall survival in AM than CM.