Melanoma Research最新文献

Using a customized, harmonized US electronic health record database, real-world prescription patterns of first-line adjuvant immunotherapy and targeted therapy were retrospectively assessed for BRAF V600-mutated melanoma. Adults with BRAF V600 mutation-positive stage IIIA-D cutaneous melanoma who received first-line adjuvant immunotherapy (nivolumab or pembrolizumab) or targeted therapy (dabrafenib plus trametinib) between 1 January 2014 and 30 August 2020 in the NOBLE database were included. Patients were followed from first-line adjuvant therapy initiation for at least 6 months, until death, progression, follow-up loss, or data cutoff. Primary endpoints were proportion of patients receiving either therapy in first-line and second-line, treatment switching, treatment timing, and status at the end of first-line therapy. Secondary endpoints included discontinuation rates, recurrence-free survival (RFS), and overall survival (OS). Of 318 patients evaluated, 67.6% received nivolumab, 14.2% pembrolizumab, and 18.2% targeted therapy as first-line adjuvant therapy. Median treatment duration was longest for nivolumab (292 days) and shortest for targeted therapy (115 days). Reason for discontinuation was recorded for 195 of 274 patients who discontinued first-line therapy; most common reasons were treatment completion and treatment-related toxicity [87/158 (55.0%) and 29/158 (18.4%), respectively, in immunotherapy-treated patients; 9/37 (24.3%) and 21/37 (56.8%) in targeted therapy-treated patients]. Median RFS and OS for targeted therapy and nivolumab were not reached and were 34.6 and 38.1 months, respectively, for pembrolizumab. These results inform on prescription preferences and clinical outcomes for BRAF V600-mutated melanoma patients in the first-line adjuvant setting.

Several studies have demonstrated that patients who experience immune-related adverse events (irAE) as a result of immunotherapy treatment, exhibit significantly improved outcomes compared to patients without toxicity. Data regarding the impact of specific irAE is, however, currently lacking. This is a real-world single-site cohort of 415 advanced melanoma patients who were treated with immunotherapy as first-line between 2014 and 2020, with a median follow-up of 24.5 months. The most frequent irAEs were cutaneous (classified as non-vitiligo, n  = 110, 26.5% and vitiligo, n  = 48, 11.6%), rheumatologic ( n  = 68, 16.4%), gastrointestinal ( n  = 66, 15.9%), endocrine ( n  = 61, 14.7%), and hepatitis ( n  = 50, 12%). Specific irAE that were significantly associated with survival benefit were rheumatologic (hazard ratio 0.34 for PFS, P  < 0.001; hazard ratio 0.38 for OS, P  < 0.001), non-vitiligo cutaneous (hazard ratio 0.58 for PFS, P  < 0.001; hazard ratio 0.54 for OS, P  = 0.001), vitiligo (hazard ratio 0.30 for PFS, P  < 0.001; hazard ratio 0.29 for OS, P  < 0.001), and endocrine (hazard ratio 0.6 for PFS, P  = 0.01; hazard ratio 0.52 for OS, P  < 0.001). Other types of irAEs, such as colitis, hepatitis and others - do not present this correlation. The occurrence of these specific irAEs may reflect a hyperactivated immune response and thus can serve as meaningful clinical biomarkers.

Mucosal melanoma is a rare melanoma subtype, accounting for about 1% of all diagnosed melanomas. It is characterized by an aggressive phenotype with a poor prognosis and a low response rate to approved treatments. We retrospectively analyzed the clinical features, treatments, and outcomes of patients diagnosed with mucosal melanoma treated with axitinib ± anti-programmed cell death protein 1 (PD-1) therapy at a single US referral center between 2018 and 2021. Radiologic response was assessed according to Response Evaluation Criteria in Solid Tumors (RECIST), v1.1. Twenty-three patients were included in this study. In all, 78% were females with a median age of 62 years. The originating site of mucosal melanoma was the sinonasal (35%), genitourinary (35%), and gastrointestinal (30%) tracts. Sixty-five percent of patients had M1c or M1d disease and 0% had BRAF V600 mutations detected. The majority (96%) had prior treatment inclusive of anti-PD-1, with a median of 2 prior lines, and 78% of patients received a combination of axitinib and PD-1 and the median duration of treatment was 3.2 months. The overall response rate was 13% and the disease control rate was 26%. The median progression-free survival was 3.2 months, and the median overall survival was 8.2 months. Overall, the regimen was well tolerated with 39% of patients requiring dose reduction and 9% requiring treatment cessation. Axitinib with anti-PD-1 therapy has modest clinical activity in heavily pretreated patients with mucosal melanoma outside of Asia, including some with long-term benefits. This data supports the worldwide clinical trials evaluating this combination and the role of incorporating vascular endothelial growth factor-based therapy in the therapeutic paradigm for patients with mucosal melanoma.

We present a case of a 75-year-old male patient who experienced a severe exacerbation of his Kaposi sarcoma lesions, which have remained clinically stable for a year, following treatment with BRAF/mitogen-activated protein kinase inhibitors for his coexisting melanoma. In this case, we present the possibility that BRAF/MEK inhibition may be mechanistically associated with the progression of Kaposi sarcoma and briefly discuss the potential mechanisms behind this phenomenon.

Eyelid melanoma (EM) is a malignant neoplasm accounting for around 1% of eyelid malignancies. Because of its rarity, most of our knowledge of EM is currently based on studies of cutaneous melanomas located elsewhere. Accordingly, this study aimed to specifically evaluate EM characteristics, management strategies, and prognosis. A retrospective study was carried out on patients diagnosed with EM at Careggi University Hospital, Florence between May 2012 and May 2022. In addition, a systematic review of relevant literature was conducted, encompassing studies published from 2013 to 2023. Clinical, histopathological, therapeutical, and prognostic data were analyzed to assess the metastasis rate and the 5-year survival rate of patients with EM. Separate data were extracted for in situ and invasive disease. Our original study included 19 patients diagnosed with EM with a 5-year survival rate of 100% for in situ and 83.3% for invasive EM. The literature review identified five poorly detailed large database reviews and 14 original studies on EM with an overall 5-year survival rate of 79.7%. The present research indicates that EM is a challenging malignancy, but has a relatively better prognosis and easier management than other melanomas of the head and neck region. These are probably related to the anatomical location which leads to early diagnosis. Therefore, EM should be considered as a specific disease requiring dedicated treatment. Based on the personal authors' experience and comprehensive overview of the current knowledge, a dedicated protocol is proposed.

This study aimed to elucidate the genetic aspects of the relationship between sex hormones and cutaneous melanoma risk, providing valuable insights into this complex association. In this study, we used estradiol, bioavailable testosterone, sex hormone-binding globulin, and total testosterone as the exposure and melanoma as the outcome for two-sample Mendelian randomization analysis. In this study, a random-effects inverse-variance weighting (IVW) model was used as the main analysis model, and the corresponding weighted median, simple mode, weighted mode, and Mendelian randomization‒Egger methods were used as supplementary methods. We assessed both heterogeneity and horizontal pleiotropy in our study, scrutinizing whether the analysis results were affected by any individual single nucleotide polymorphism. The random-effects IVW method indicated that estradiol [odds ratio (OR), 1.000; 95% confidence interval (CI), 0.998-1.003; P  = 0.658], bioavailable testosterone (OR = 1.001, 95% CI, 0.999-1.003; P  = 0.294), sex hormone-binding globulin (IVW: OR, 1.000; 95% CI, 0.998-1.003; P  = 0.658), and total testosterone (IVW: OR, 1.002; 95% CI, 0.999-1.005; P  = 0.135) were not genetically linked to cutaneous melanoma. No analyses exhibited heterogeneity, horizontal pleiotropy, or deviations. We were unable to find genetic evidence for a causal relationship between sex hormones and the occurrence of cutaneous melanoma in this study. These results are limited by sample size and population, so the causal relationship between sex hormones and cutaneous melanoma needs to be further studied.

Hemophagocytic lymphohistiocytosis (HLH) has been reported rarely with BRAF/MEK inhibitor combinations, including dabrafenib/trametinib. Postmarketing pharmacovigilance analyses evaluating outcomes associated with dabrafenib/trametinib-induced HLH are also lacking. Herein, we report a case of dabrafenib/trametinib-induced HLH in a patient with metastatic melanoma. Recovery of HLH-related symptoms was observed following drug discontinuation, supportive care, and corticosteroids. We also conducted a pharmacovigilance analysis of the USA Food and Drug Administration Adverse Event Reporting System (FAERS) to describe postmarketing cases of HLH with dabrafenib/trametinib exposure. There were 50 reports of HLH with dabrafenib/trametinib in FAERS. Most cases occurred in the setting of melanoma ( n  = 39; 78%) and most were reported in Europe ( n  = 39; 74%). Hospitalization was the most common outcome ( n  = 39; 78%) of this adverse event per FAERS. HLH is a rare complication of dabrafenib/trametinib, and clinicians should be aware and monitor for signs of this potentially serious and life-threatening adverse event.

Melanoma is the most serious and deadly form of skin cancer and with progression to advanced melanoma, the intrinsically disordered protein α-synuclein is upregulated to high levels. While toxic to dopaminergic neurons in Parkinson's disease, α-synuclein is highly beneficial for primary and metastatic melanoma cells. To gain detailed insights into this exact opposite role of α-synuclein in advanced melanoma, we performed proteomic studies of high-level α-synuclein-expressing human melanoma cell lines that were treated with the diphenyl-pyrazole small-molecule compound anle138b, which binds to and interferes with the oligomeric structure of α-synuclein. We also performed proteomic and transcriptomic studies of human melanoma xenografts that were treated systemically with the anle138b compound. The results reveal that interfering with oligomerized α-synuclein in the melanoma cells in these tumor xenografts led to a substantial upregulation and expression of major histocompatibility complex proteins, which are pertinent to enhancing anti-melanoma immune responses.