Immune checkpoint inhibitor‐based therapy for advanced acral and mucosal melanoma

Abstract

The advent of immune checkpoint inhibitors (ICIs) including anti-PD-1 (pembrolizumab and nivolumab) and anti-CTLA-4 (ipilimumab) antibodies drastically changed treatment modalities for patients with various kinds of cancers, including lung cancer, 1 breast cancer, 2 oesophageal cancer, 3 urothelial cancer, 4 cervical cancer, 5 endometrial cancer, 6 renal cell carcinoma, 7,8 head and neck cancer, 9 Hodgkin lymphoma, 10 high microsatellite instability/ mismatch repair-deficient cancer, 11,12 tumour mutational burden (TMB)-high solid cancer, 13 and melanoma, 14,15 in advanced and/or adjuvant stage. ICIs are commonly used for treating advanced cutaneous melanoma (CM). In the phase III KEYNOTE-006 clinical trial, pembrolizumab resulted in an objective response rate (ORR) of 42% and a longer overall survival (OS) than ipilimumab (median OS: 32.7 months vs. 15.9 months; p < 0.001). 16 Likewise, the randomized phase III CheckMate-067 clinical trial demonstrated that nivolumab plus ipilimumab resulted in a better ORR and prolonged survival than nivolumab alone (ORR, 58% vs. 45%; median progression-free survival (PFS), 11.5 months vs. 6.9 months; median OS, not reached vs. 36.9 months). 17 Moreover, the 5-year OS has improved from <10% in patients with advanced stage CM treated with conventional chemotherapy, such as dacarbazine, to 30%-50%, especially in patients treated with anti-PD-1 antibody alone or in combination with ipilimumab. 16,18,19 CM is predominantly manifested in the sun-exposed skin of the Caucasian population. 20 However, melanomas rarely

Mucosal Melanoma Clinical Management and Prognostic Implications: A Retrospective Cohort Study

“…Adjuvant systemic therapy options for MM are limited, with systemic therapy for CM often recommended [ 43 ]. MM’s lower mutational burden and reduced PD-L1 expression might explain their relatively poorer response to immunotherapy compared to CM [ 8 , 23 , 40 ].…”

Safety and efficacy of Pucotenlimab (HX008) - a humanized immunoglobulin G4 monoclonal antibody in patients with locally advanced or metastatic melanoma: a single-arm, multicenter, phase II study

“…10 The Affiliated Cancer Hospital of Xinjiang Medical University, Ürümqi, China. 11 Taizhou Hanzhong Biomedical Co., Ltd.…”

“…Due to the rarity of acral and mucosal melanoma, especially in the Caucasian population, and the different biological features, the efficacies of the approved immune checkpoint inhibitors reported in acral and mucosal melanoma were underexplored and inconsistent compared with those reported in cutaneous melanoma. Based on a series of clinical trials with small sample sizes, the ORRs were 11.4 ~ 34% and 3.9 ~ 35% for acral melanoma and mucosal melanoma, respectively, and the corresponding median PFS were 2.1 ~ 6.6 months and 1.4 ~ 9 months [11]. Pucotenlimab is a novel, fully-humanized monoclonal antibody which selectively blocks the interaction between PD-1 and its ligands [12].…”

Clues for developing next‐generation cancer immunotherapy

“…Therefore, information derived from TRs using durable responders' samples may provide clues for tumour rejection by T cells. Mori et al 9 reviewed the current status of ICIs in clinical practice, especially focusing on acral and mucosal melanoma. Since these subtypes are rare in the Caucasian population, there have been few data with reliable sample sizes.…”

“…Mori et al 9 reviewed the current status of ICIs in clinical practice, especially focusing on acral and mucosal melanoma. Since these subtypes are rare in the Caucasian population, there have been few data with reliable sample sizes.…”