Managing Metastatic Melanoma in 2022: A Clinical Review

Cutaneous melanoma remains the most lethal of the primary cutaneous neoplasms, and although the incidence of primary melanoma continues to rise, the mortality from metastatic disease remains unchanged, in part through advances in treatment. Major developments in immunomodulatory and targeted therapies have provided robust improvements in response and survival trends that have transformed the clinical management of patients …
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Melanoma brain metastases: Biological basis and novel therapeutic strategies

The development of brain metastases is the deadliest complication of advanced melanoma and has long been associated with a dismal prognosis. The recent years have seen incredible progress in the development of therapies for melanoma brain metastases (MBM), with both targeted therapies (the BRAF-MEK inhibitor combination) and immune checkpoint inhibitors (the anti-CTLA-4, anti-PD-1 combination) …
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Relatlimab and Nivolumab versus Nivolumab in Untreated Advanced Melanoma

Lymphocyte-activation gene 3 (LAG-3) and programmed death 1 (PD-1) are distinct inhibitory immune checkpoints that contribute to T-cell exhaustion. The combination of relatlimab, a LAG-3-blocking antibody, and nivolumab, a PD-1-blocking antibody, has been shown to be safe and to have antitumor activity in patients with previously treated melanoma, but the safety and activity in patients with previously untreated melanoma need investigation …
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Randomized Phase III Trial Evaluating Spartalizumab Plus Dabrafenib and Trametinib for BRAF V600-Mutant Unresectable or Metastatic Melanoma

Preclinical data suggest the combination of an anti-programmed death receptor 1 antibody plus dabrafenib and trametinib to have superior antitumor activity compared with dabrafenib plus trametinib alone. These observations are supported by translational evidence suggesting that immune checkpoint inhibitors plus targeted therapy may improve treatment outcomes in patients with BRAF V600-mutant metastatic melanoma …
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T cell characteristics associated with toxicity to immune checkpoint blockade in patients with melanoma

Severe immune-related adverse events (irAEs) occur in up to 60% of patients with melanoma treated with immune checkpoint inhibitors (ICIs). However, it is unknown whether a common baseline immunological state precedes irAE development. Here we applied mass cytometry by time of flight, single-cell RNA sequencing, single-cell V(D)J sequencing, bulk RNA sequencing and bulk T cell receptor (TCR) sequencing to study …
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