Optimal strategy in managing advanced melanoma

Abstract

The advent of immune checkpoint inhibitors and combination therapy with BRAF inhibitors and MEK inhibitors has dramatically improved the prognosis of advanced melanoma. However, since acral melanoma and mucosal melanoma, which are rare in Western countries but are major subtypes of melanoma in East Asia, including Japan, have a low frequency of BRAF mutations, there are currently no treatment options other than immune checkpoint inhibitors in most such cases. Furthermore, owing to a lower tumor mutation burden, immune checkpoint inhibitors are less effective in acral and mucosal melanoma than in cutaneous melanoma. The aim of this review was to summarize the current status and future prospects for the treatment of advanced melanoma, comparing cutaneous melanoma, acral melanoma, and mucosal melanoma.

Malignant Melanoma: An Overview, New Perspectives, and Vitamin D Signaling

“…In the case of a positive for melanoma sentinel lymph node biopsy (SLNB), some surgeons are offering elective lymph nodes dissection, which is, however, connected with increased morbidity and does not improve the OS [ 30 , 48 , 189 , 190 ]. For high risk of development of metastatic disease stages IIB and C, and when SLNB is positive, adjuvant postsurgical therapy can be applied with some limitations that either include immunotherapy using immune check point inhibitors (ICIs) or targeted therapy [ 30 , 48 , 191 ]. However, the majority of experts acknowledge that the serious adverse side effects may outweigh potential benefits for stage IIB/C and perhaps some IIIA patients (positive SLNB) vs. clinical observation [ 192 ].…”

“…This is in addition to the high costs of such therapies. The attendant toxicity of immunotherapy in melanoma patients is well documented [ 48 , 191 , 192 , 193 ]. Therefore, gene profile testing (GEP) promises to help which subsets of stage IIB/C would benefit from adjuvant therapy [ 192 ].…”

“…Interestingly, T-cell gene signatures derived from inflammatory skin diseases, such as systemic lupus erythematous (SLE) or psoriasis, can provide potential biomarkers for predicting the response to immune checkpoint blockade therapy in melanoma [ 194 ]. Stage III and IV melanoma patients are the subjects of immunotherapy, targeted therapy, or combined therapy [ 30 , 48 , 191 , 192 , 193 , 195 , 196 , 197 ].…”

“…The currently approved immunotherapy approaches involve targeting with antibodies the following ICIs: cytotoxic T lymphocyte-associated antigens 4 (CTLA-4), programmed cell death 1 (PD-1), PD ligand 1 (PDL-1), and lymphocyte-activation gene 3 (LAG3), with a combination of the antibodies if necessary, or in combination with other treatments [ 18 , 30 , 36 , 46 , 48 , 191 , 192 , 193 , 195 , 196 , 197 , 210 ]. They appear to be effective in a certain subset of patients [ 211 ].…”

“…Also, an adverse phenomenon of hyperprogression described in ICI therapy in solid tumors [ 212 , 213 ] is very rare in melanomas [ 214 ]. In the past, several immunotherapeutic approaches were tested, including the use of peptide from melanogenesis-related proteins, dendritic cells, tumor-infiltrating lymphocytes (TIL), adoptive T-cell therapy (ACT), interleukin 2, and interferons [ 215 , 216 , 217 , 218 ], none of which were sufficiently effective in phase 3 clinical trials [ 30 , 191 ]. Tumor-infiltrating lymphocyte (TIL) therapy for patients with advanced-stage melanoma have been reviewed in-depth recently [ 218 ].…”