Melanoma Research最新文献

Patients diagnosed with melanoma are at an elevated risk of developing subsequent primary melanomas. The aim of this study was to assess the prevalence and identify the risk factors associated with multiple primary melanomas (MPMs) in patients referred to the melanoma outpatient service of the Dermatology Unit at the University Hospital of Udine, Italy. We conducted a retrospective analysis on patients with MPMs. For each patient demographic, clinical, and histological data were collected. For each excised melanoma, we recorded Breslow thickness, histological subtype, and anatomical site. A total of 233 patients with melanoma were included in the study, comprising a subgroup of 51 (22%) patients diagnosed with MPM. The mean Breslow thickness for patients with a single melanoma was significantly higher than the Breslow thickness for the first melanoma in the MPM subgroup. Furthermore, a statistically significant decrease in Breslow thickness between the first and second melanomas was observed. In our cohort, patients with MPM had a significantly higher prevalence of nonmelanoma skin cancers (NMSCs) compared with those with a single melanoma. Our study indicates that the prevalence of MPM in the province of Udine is among the highest reported globally. Our finding aligns with the broader literature, which consistently reports lower thickness in second melanoma compared with first melanoma. Finally, the higher prevalence of NMSC in these patients suggests a potential link to chronic ultraviolet exposure.

While the association between chronic lymphocytic leukemia (CLL) and a higher incidence of melanoma is well documented, the diagnosis of concurrent high-risk chronic myelomonocytic leukemia (CMML) and metastatic melanoma (MM) has not previously been described. Moreover, the treatment of MM and CMML differ greatly in the mechanism of action of their corresponding antineoplastic therapies: treatment of MM frequently involves immune checkpoint inhibitors (ICI), while patients with CMML receive myelosuppressive agents. Simultaneous management of these malignancies can be nuanced due to the potential impact of one treatment's constituents on the activity of the other and the broad and nonoverlapping array of potential adverse effects of these agents. Here, we describe the clinical course of a patient who was diagnosed with concurrent MM and CMML and our approach to the challenging balance of delivering ICI concurrently with the hypomethylating agent azacitidine and the BCL-2 inhibitor venetoclax.

Myeloid-derived suppressor cells (MDSCs) are expanded in cancer patients, have an intrinsic immunosuppressive function, and thus may play a role in resistance to immunotherapy. Ulceration of the melanoma primary is associated with more aggressive disease and is an independent prognostic factor for melanoma-specific survival. However, the underlying factors contributing to this more aggressive phenotype are not completely understood. The current study aims to correlate changes in circulating MDSC during immunotherapy in patients with ulcerated vs non-ulcerated melanoma primary tumors. Longitudinal changes in levels of circulating MDSCs were analyzed via flow cytometry in melanoma patients receiving immune checkpoint inhibitors (ICIs) and stratified by ulceration status. Following the initiation of therapy, the percentage of total MDSCs increased significantly in patients with both ulcerated ( P  = 0.003) and non-ulcerated ( P  < 0.001) tumors. When MDSCs were stratified by subset, the proportion of granulocytic MDSC (PMN-MDSC) decreased in patients with non-ulcerated tumors ( P  = 0.023), while the proportion remained stable in patients with ulcerated tumors ( P  = 0.121). The reduction in the proportion PMN-MDSC in non-ulcerated patients coincided with a statistically significant increase in the proportion of CD14 + /CD15 + MDSC ( P  = 0.008), resulting in a greater proportion of CD14 + /CD15 + MDSC in non-ulcerated patients as compared to ulcerated melanoma patients following two infusions of ICIs (27.3 ± 19.2% vs 16.1 ± 19.2%; P  = 0.008). The trajectories of the MDSC populations described here provide insight into the altered tumor microenvironment in ulcerated melanoma and highlight key changes in a cell population that could contribute to immunotherapy resistance.

BRAF and MEK inhibitor (BRAFi + MEKi) therapy has improved the treatment of solid tumors with BRAF mutation. However, their neurologic adverse events (nAEs) have been largely unexplored. This study aimed to provide clinicians with more updated knowledge on nAEs associated with BRAFi + MEKi therapy in patients with malignant melanoma compared with nonmelanoma cancers. The United States Food and Drug Administration Adverse Event Reporting System was queried from 2011 to 2022 to capture nAEs reported for the BRAFi + MEKi therapies, vemurafenib plus cobimetinib (V + C), dabrafenib plus trametinib (D + T), and encorafenib plus binimetinib (E + B). A disproportionality analysis was performed to calculate their reporting odds ratios (RORs) and 95% confidence intervals (CIs) using a control group of antineoplastic medications. There were 2881 BRAFi + MEKi therapy-associated nAE cases, the majority of which listed malignant melanoma as the reason for use (87.5, 66.7, and 62.0% for V + C, D + T, and E + B, respectively). Several novel associations were identified; including epidural lipomatosis (ROR: 320.07, 95% CI: 123.76-827.77 for V + C), peripheral nerve lesion (ROR: 185.64, 95% CI: 73.95-466.03 for V + C), Guillain-Barre syndrome (RORs: 8.80, 2.94, and 11.79, 95% CIs: 3.65-21.22, 1.40-6.19, and 5.87-23.66 for V + C, D + T, and E + B), demyelinating polyneuropathy (RORs: 24.72 and 78.98, 95% CI: 8.16-74.86 and 24.84-251.13 for D + T and E + B), and multiple sclerosis (ROR: 5.90, 95% CI: 3.06-11.40 for D + T) in melanoma patients. nAEs in the setting of BRAFi + MEKi therapy should be a safety consideration when utilizing these medications.

Malignant melanoma is a broad and heterogeneous class of malignant tumors derived from melanocytes and classified as cutaneous (skin), uveal, and mucosal melanoma. The incidence of melanoma has increased worldwide in recent decades. Surgery remains the mainstay of treatment, but a dramatic change in systemic treatment occurred when immune checkpoint inhibitors (ICIs) entered the therapeutic armamentarium for metastatic melanoma. Pembrolizumab and nivolumab, both anti-programmed death antibodies, demonstrated superiority over standard therapies with a 5-year survival rate. Toxicities resulting from ICIs have an autoimmune etiology and can affect any organ system. We then present a case of a patient with metastatic melanoma treated with an ICI strategy who developed endocrine toxicity such as the syndrome of inappropriate antidiuresis (SIAD). A previous case report concerning an anti-programmed death ligand 1 antibody suggests that this pathway may be involved in the development of SIAD.

The objective of this study was to provide an overview of the current practice of patient-reported outcome (PRO) assessments in trials investigating treatment with BRAF inhibitors in patients with advanced melanomas. In addition, we extracted information on symptomatic adverse events (AEs) reported by clinicians to inform future PRO measurement strategies. For our systematic scoping review, we investigated randomized controlled trials (RCTs) evaluating treatment with BRAF inhibitors that had a primary, secondary or exploratory PRO endpoint and were indexed on PubMed. Two independent reviewers extracted information on general RCT characteristics, clinical results (e.g. survival, treatment response and symptomatic AEs) and the PRO measurement and results. Quality of PRO reporting using the CONSORT-PRO checklist was also assessed. We identified nine RCTs meeting the inclusion criteria, in which PROs were secondary or exploratory endpoints. In all trials but one, PROs were measured with the generic EORTC QLQ-C30 questionnaire. The quality of PRO reporting showed substantial variation across the different types of information, with information on handling of missing data and on PRO hypotheses lacking most frequently. Our analysis identified 29 relevant symptomatic AEs that could be reported directly by patients. Our findings may inform the planning of the PRO component of future RCTs, in particular regarding what symptoms and AEs should be covered by PRO measures to provide a comprehensive assessment of treatment tolerability. Our results also indicate a need for improving the quality of PRO reporting, to maximize the impact of PRO findings in real-word practice.

Acquired generalized lipodystrophy (AGL) is a rare complication of immune checkpoint inhibitors (ICIs) and is associated with immune-mediated loss of adipose tissue, peripheral resistance to insulin, and serious metabolic complications. Here we report a new case of ICI-induced AGL and provide an updated literature review of published cases. We report a 39-year-old female patient treated with adjuvant pembrolizumab for stage IIIC nevoid melanoma with ICI-induced AGL. After six cycles of pembrolizumab, she developed a 40 lb weight loss with fat wasting, a decreased leptin level, significant liver function abnormalities, hepatic steatosis, hypertriglyceridemia, and subsequently was found to have severe insulin dependence and resistance. No corticosteroids were given and pembrolizumab was discontinued. AGL persists at 3-year follow up and patient remains free of melanoma progression. Literature review identified an additional seven patients who developed ICI-induced acquired lipodystrophy, predominantly female. Of the identified cases, three patients received steroids without resolution of their acquired lipodystrophy, while one patient had resolution without steroid treatment. Five patients and our case were treated with ICIs for melanoma, and all had at least a partial response to treatment. ICI-induced acquired lipodystrophy is an exceedingly rare event with profound clinical consequences. Our case report and literature review better characterized the clinical course and treatment outcomes of these patients. With the increasing utilization of ICIs in treating cancer, further studies to better understand the underlying mechanism and to guide clinical management of the metabolic complications are needed.

Temozolomide is used in melanoma therapy, but the comparative efficacy and safety of monotherapy vs combination therapies are unclear. This meta-analysis evaluates temozolomide monotherapy vs combination therapies in melanoma patients. PubMed, Embase, and Cochrane Library were searched up to August 2024 for studies comparing temozolomide monotherapy with combination therapies in melanoma. Primary outcomes were 1-year survival and objective response rates (RR); secondary outcomes included hematologic and non-hematologic toxicities. Data were pooled using risk ratios with 95% confidence intervals (CIs). Seven studies were included. Combination therapies improved objective RR over temozolomide monotherapy (risk ratio 0.68, 95% CI: 0.53-0.88). One-year survival did not differ significantly between groups (risk ratio 0.81, 95% CI: 0.59-1.12). Temozolomide monotherapy was associated with reduced incidence of leukopenia (risk ratio 0.54, 95% CI: 0.30-0.95). Adding interferon-alpha (IFN-α) to temozolomide significantly improved 1-year survival (risk ratio 0.54, 95% CI: 0.35-0.84) and objective RR (risk ratio 0.57, 95% CI: 0.42-0.78) compared to temozolomide alone, without significantly increasing toxicity. Combination therapies enhance objective RR over temozolomide monotherapy, with similar 1-year survival. Temozolomide monotherapy offers a better hematologic safety profile. Combining temozolomide with IFN-α significantly improves survival and RR without increasing toxicity. Clinicians should balance efficacy and safety when choosing melanoma treatments.

Vitiligo-like hypopigmentation induced by immune checkpoint inhibitors (ICIs) has been largely associated with improved survival outcomes in metastatic melanoma. However, its development during adjuvant ICI therapy and its role as a prognostic factor in this setting remain unclear. We aimed to describe ICI-induced vitiligo in a cohort of patients with resected stage III melanoma treated with adjuvant ICI and to identify differences in progression-free survival (PFS) and distant metastasis-free survival (DMFS) between those who developed vitiligo and those who did not. Patients and data were collected from two institutions, both retrospectively and prospectively, from January 2018 to February 2024. Patients were divided into 'vitiligo' and 'non-vitiligo' groups for comparisons. Of 40 patients, 22.5% developed ICI-induced vitiligo [median follow-up: 23 months (1-73)]. Treatments received were nivolumab (70%) and pembrolizumab (30%). Fifty-five percent of the patients completed 1 year of treatment, 37.5% discontinued and 7.5% were still ongoing. Vitiligo and non-vitiligo groups differed in the cause of treatment discontinuation (severe toxicity in vitiligo vs. progression in non-vitiligo, P  = 0.005) and the occurrence of progression (none in vitiligo vs. 52% in non-vitiligo, P  = 0.001). Survival analyses showed longer PFS in vitiligo group ( P  = 0.013) and no differences in DMFS ( P  = 0.111). ICI-induced vitiligo typically affected photo-exposed areas, with a median time to onset of 4 months (1-27). These preliminary results on ICI-induced vitiligo in adjuvant treatment are in agreement with those reported in advanced melanoma treatment, so its development in the adjuvant setting could be a sign of good prognosis as well.