A Phase Ib Study of Pembrolizumab as Second-Line Therapy for Chinese Patients With Advanced or Metastatic Melanoma (KEYNOTE-151).

Acral and mucosal melanomas are extremely rare in Caucasians; however, they are the predominant melanoma subtypes in Asians and other non-Caucasian populations. Acral and mucosal melanomas share many clinicopathological features, including aggressive phenotypes, similar genetic landscapes, and grim prognoses. In spite of advances in melanoma management, patients with acral and mucosal melanomas show limited benefit from current therapies. The rarity of these subtypes of melanoma is a significant factor contributing to the poor understanding of these pathological subtypes and the lack of effective interventions. Furthermore, the mechanisms contributing to disparities between different types of melanoma remain largely unclear. Herein, we comprehensively review current knowledge on the clinicopathological characteristics and mutational landscapes of acral and mucosal melanomas, as well as providing an overview of current therapies for patients with these aggressive melanoma subtypes, focusing on available immunotherapeutic interventions. We also discuss pathological differences between different melanoma subtypes and summarize current knowledge on melanoma disparities between Asians and Caucasians. Finally, we discuss emerging immunotherapeutic strategies for the treatment of acral and mucosal melanomas, focusing on combination therapies with immune checkpoint inhibitors. Unraveling the unique features of acral and mucosal melanomas is key for their early diagnosis and for the development of effective therapies.

Immunotherapy in Acral and Mucosal Melanoma: Current Status and Future Directions.

Background:Conventional cytotoxic chemotherapy offers minor benefit to patients with mucosal melanoma (MM). Although immune checkpoint inhibitors (ICIs) have become the preferred approach in patien...

https://journals.sagepub.com/doi/pdf/10.1177/1758835920922028

Immune checkpoint inhibitors in advanced or metastatic mucosal melanoma: a systematic review:

BACKGROUND The tumor microenvironment (TME) is critical in the progression and metastasis of skin cutaneous melanoma (SKCM). Differences in tumor-infiltrating immune cells (TICs) and their gene expression have been linked to cancer prognosis. Given that immunotherapy can be effective against SKCM, we aimed to identify key genes that regulate the immunological state of the TME in SKCM. METHODS Data from 471 SKCM patients in the The Cancer Genome Atlas were analyzed using ESTIMATE algorithms to generate an ImmuneScore, StromalScore, and EstimateScore for each patient. Patients were classified into low- or high-score groups based on median values, then compared in order to identify differentially expressed genes (DEGs). Then a protein-protein interaction (PPI) network was developed, and a prognostic model was created using uni- and multivariate Cox regression as well as the least absolute shrinkage and selection operator (LASSO). Key DEGs were identified using the web-based tool GEPIA. Profiles of TIC subpopulations in each patient were analyzed using CIBORSORT, and possible correlations between key DEG expression and TICs were explored. Levels of CCL8 were determined in SKCM and normal skin tissue using immunohistochemistry. RESULTS Two scores correlated positively with the prognosis of SKCM patients. Comparison of the low- and high-score groups revealed 1684 up-regulated and 18 down-regulated DEGs, all of which were enriched in immune-related functions. The prognostic model identified CCL8 as a key gene, which CIBERSORT found to correlate with M1 macrophages. Immunohistochemistry revealed strong expression in SKCM tissue, but failed to detect the protein in normal skin tissue. CONCLUSIONS CCL8 is a potential prognostic marker for SKCM, and it may become an effective target for melanoma in which M1 macrophages play an important role.

Correlation of CCL8 expression with immune cell infiltration of skin cutaneous melanoma: potential as a prognostic indicator and therapeutic pathway.

Single-agent anti-PD-1 or combined with ipilimumab in patients with mucosal melanoma: an international, retrospective, cohort study.

Malignant melanoma is one of the most common malignancies. Its incidence grows rapidly at an annual rate of 3−5%. Although the incidence of melanoma remains low in China, it has increased rapidly, with approximately 20,000 new cases reported each year. The mortality of melanoma also has been increasing rapidly; in contrast, although the incidence of melanoma is also increasing in western countries, its mortality basically remains unchanged and does not rise along with the escalation in prevalence. Thus, there is still a wide gap between China and Western countries in the diagnosis and treatment of melanoma. Melanoma has become one of the diseases that pose a major threat to health of Chinese people. However, compared with other common malignant tumors, there is still a far way to go to achieve the standardized diagnosis and treatment of melanoma. In May 2007, the Chinese Society of Clinical Oncology (CSCO) formally established the CSCO Melanoma Panel with an attempt to promote the development of clinical oncology, facilitate the multidisciplinary standardized treatment for melanoma, advocate the active learning and application of currently available scientific evidences at home and abroad, and explore the development of Chinese guidelines on the clinical practices on melanoma. After consultations with multidisciplinary experts, the first edition of the Chinese Consensus on the Diagnosis and Treatment of Melanoma was released in 2008; in 2009, 2011, and 2013, three revisions of this consensus document were published after many multidisciplinary seminars. The past 5 years have witnessed several breakthroughs in the clinical treatment of melanoma. Melanoma has become one of the malignant tumors whose treatment patterns have changed rapidly. To adapt to the fast advances in melanoma treatment and make the clinical management of melanoma in China more standardized and internationalized, the 2015 edition of the Chinese Guidelines on the Diagnosis and Treatment of Melanoma was finalized after repeated and wide consultations with multidisciplinary experts and updated and added with much new information, with an attempt to provide the up-todated and reliable instructions on clinical practices based recent scientific evidences.

/pdf/chinese-guidelines-on-the-diagnosis-and-treatment-of-3uw3729uzv.pdf

Chinese Guidelines on the Diagnosis and Treatment of Melanoma (2015 Edition)

Malignant melanoma is one of the most common malignancies. Its incidence grows rapidly at an annual rate of 3−5%. Although the incidence of melanoma remains low in China, it has increased rapidly, with approximately 20,000 new cases reported each year. The mortality of melanoma also has been increasing rapidly; in contrast, although the incidence of melanoma is also increasing in western countries, its mortality basically remains unchanged and does not rise along with the escalation in prevalence. Thus, there is still a wide gap between China and Western countries in the diagnosis and treatment of melanoma. Melanoma has become one of the diseases that pose a major threat to health of Chinese people. However, compared with other common malignant tumors, there is still a far way to go to achieve the standardized diagnosis and treatment of melanoma. In May 2007, the Chinese Society of Clinical Oncology (CSCO) formally established the CSCO Melanoma Panel with an attempt to promote the development of clinical oncology, facilitate the multidisciplinary standardized treatment for melanoma, advocate the active learning and application of currently available scientific evidences at home and abroad, and explore the development of Chinese guidelines on the clinical practices on melanoma. After consultations with multidisciplinary experts, the first edition of the Chinese Consensus on the Diagnosis and Treatment of Melanoma was released in 2008; in 2009, 2011, and 2013, three revisions of this consensus document were published after many multidisciplinary seminars. The past 5 years have witnessed several breakthroughs in the clinical treatment of melanoma. Melanoma has become one of the malignant tumors whose treatment patterns have changed rapidly. To adapt to the fast advances in melanoma treatment and make the clinical management of melanoma in China more standardized and internationalized, the 2015 edition of the Chinese Guidelines on the Diagnosis and Treatment of Melanoma was finalized after repeated and wide consultations with multidisciplinary experts and updated and added with much new information, with an attempt to provide the up-to-dated and reliable instructions on clinical practices based recent scientific evidences.

Chinese Guidelines on the Diagnosis and Treatment of Melanoma (2015 Edition).

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Chinese Guidelines on the Diagnosis and Treatment of Melanoma (2015 Edition)

Chinese Guidelines on the Diagnosis and Treatment of Melanoma (2015 Edition).