Journal of Clinical and Aesthetic Dermatology • Hot Topics in Melanoma July 2025 • JOURNAL WATCH

☛ In the digital edition, click the PMID after each summary to access the article/abstract.

Upregulated m7G methyltransferase METTL1 is a potential biomarker and tumor promoter in skin cutaneous melanoma

Summary. In cutaneous melanoma samples, methyltransferase-like 1 (METTL1) was significantly upregulated, and patients with high expression had worse survival outcomes compared to those with low expression. Melanoma cell viability, migration, and invasion were significantly inhibited with METTL1 knockdown. Further analysis showed a negative correlation between METTL1 and CD8A, a marker for CD8+ T cell expression. High expression of METTL1 led to reduced CD8+ T cell infiltration, thereby potentially contributing to tumor progression. Evaluating data from patients treated with anti-programmed cell death protein 1 (PD-1) immune checkpoint inhibitors (ICIs), researchers found that high METTL1 expression was associated with significantly poorer prognosis.

Neoadjuvant cobimetinib and atezolizumab with or without vemurafenib for Stage III melanoma: outcomes and the impact of the microbiome from the NeoACTIVATE trial

Summary. In the Phase II NeoACTIVATE trial, 14 patients had BRAF-wildtype melanoma and received cobimetinib and atezolizumab (cohort A), and 13 had BRAF-mutated melanoma and received cobimetinib and atezolizumab with vemurafenib (cohort B). In cohort A, median recurrence-free survival (RFS) was not reached, and 57.1 percent of patients were alive without recurrence at 24 months. Median RFS was 40.8 months for cohort B, with 69.2 percent of patients being recurrence-free at 24 months. Microbial metabolic pathway of arginine biosynthesis and pathway of unsaturated fatty acid biosynthesis were significantly reduced in patients with early distant metastasis. Transient decreases in CD4+CD8+ T cells occurred at neoadjuvant treatment imitation in both cohorts; cohort B also showed transient decreases in CD4+ T cells.

Patient-reported outcomes with adjuvant nivolumab versus placebo after complete resection of Stage IIB/C melanoma in the randomized Phase III CheckMate 76K trial

Summary. Evaluating patient-reported outcome data from patients with Stage IIB/C melanoma enrolled in the CheckMate 76K trial, Kirkwood et al found that health-related quality of life did not undergo clinically meaningful change from baseline in either the nivolumab (n=523) or placebo (n=264) groups. Time to confirmed deterioration was not significantly different between treatment groups for European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ-C30) subscales. For the EuroQoL 5-Dimension 5-Level (EQ-5D- 5L) visual analog scale (VAS), the nivolumab group experienced shorter time to confirmed deterioration, compared to the placebo group. Side effects of any level of bother were reported in 25 to 43 percent of patients in the nivolumab group and 21 to 28 percent of patients in the placebo group during the treatment period. The rate of severe bother was low in both treatment groups.

Gaps in the management of adrenal insufficiency in melanoma survivors: a retrospective cohort study

Summary. Fifty-five percent of patients with melanoma who developed ICI-induced secondary adrenal insufficiency (SAI) received prednisone as initial glucocorticoid replacement, compared to 27 percent of those with pituitary adenoma–related SAI. Compared to patients with ICI-induced SAI, patients with pituitary adenoma–related SAI received significantly lower median initial doses of hydrocortisone and prednisone; maintenance hydrocortisone dose was also significantly lower in the pituitary adenoma–related SAI group. The ICI-related SAI group had significantly higher median distress score versus the pituitary adenoma–related SAI group, and patients with melanoma and ICI-related SAI also showed greater incidence of anxiety, fatigue, and pain. Survival outcomes were reduced with prednisone versus hydrocortisone use among patients with melanoma and ICI-related SAI.

Novel treatment vs. standard of care in melanoma-associated leptomeningeal metastases: a systematic review and network meta-analysis

Summary. Researchers reviewed seven studies (4 retrospective cohort, 2 observational cohort, 1 clinical trial) on various treatment methods for melanoma with leptomeningeal disease. Immunotherapy plus targeted therapy was found to be the most effective treatment compared to systemic therapy plus radiotherapy (log hazard ratio [logHR]: –2.52; p=0.003). Immunotherapy alone also demonstrated improved outcomes over systemic therapy plus radiotherapy (logHR: –2.03; p=0.009). However, quality of the included studies ranged from low to very low, and there was moderate-to-severe risk of bias. Heterogeneity between studies was low (I2=13.4%).

Early switch from run-in with targeted to immunotherapy in advanced BRAF^V600-positive melanoma: final results of the randomized Phase II ImmunoCobiVem trial

Summary. In this Phase II trial, patients with BRAF^V600-positive advanced/metastatic melanoma participated a three-month run-in phase with oral vemurafenib and cobimetinib and were then randomized to continue with targeted therapy (arm A) or receive atezolizumab (arm B). PFS from run-in initiation to first documented disease progression was significantly higher in arm A versus arm B (median: 13 vs. 5.9 months). Median overall survival (OS) was 40.2 months in arm A and 49.6 months in arm B; 48- and 60-month OS rates were greater in arm B (52.6% and 45.0%, respectively), compared to arm A (42.4% and 40.1%, respectively). After treatment crossover, total PFS was slightly improved in arm B versus arm A (14.6 vs. 12.6 months). Diarrhea was the most frequent treatment-related adverse event (TRAE). The rate of grade 3 to 4 TRAEs was 42.0 and 48.5 percent in arms A and B, respectively.

Secondary intention healing after functional surgery for melanoma of the nail apparatus: functional, cosmetic, and patient satisfaction results

Stevens J, Céspede-Núñez M. Skin Appendage Disord. 2025:1–8. Epub ahead of print.

Summary. In this study, two patients with minimally invasive nail melanoma and four with nail melanoma in situ underwent secondary intention healing following functional surgery. One patient experienced severe postoperative pain, and one patient had nail spicule formation. Mean time to complete granulation tissue coverage and complete re-epithelialization was 2.83 and 8.45 weeks, respectively. Patient-reported outcomes were measured at 12 weeks postsurgery. Mean VAS score for pain was two. Mean Dermatology Quality Life Index (DLQI) score was two. Patients showed a mean Quick Disabilities of the Arm, Shoulder, and Hand (Quick-DASH) functionality score of 18.92 percent. Cosmetic outcomes were measured with the Vancouver Burn Scar Assessment Scale (VBSAS), and mean score was 2.8 at Week 12.

In this retrospective observational study, researchers assessed the utility of ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography ([¹⁸F]-FDG PET/CT) in malignant melanoma. Forty-eight patients were included for analysis. Breslow thickness and ulceration were significantly associated with presence of metastases (both p=0.01), and ulceration was also associated with pulmonary metastases (p=0.02). Presence of intra-abdominal metastases showed a significant correlation with both perineural (p<0.001) and vascular (p=0.0007) invasion. Tumor-infiltrating lymphocytes were negatively associated with intra-abdominal metastases (p=0.05). Sentinel lymph node positivity was associated with regional and overall presence of metastases (p=0.008 and p=0.02, respectively). Additionally, subcutaneous standardized uptake values significantly differed between male and female patients.

Source: Mititelu TS, Mititelu MR, Bucurica S, Costache DO. [¹⁸F]-FDG PET/CT in malignant melanoma. Diagnostics (Basel). 2025;15(10):1192.

RESEARCH BITE—Longitudinal genomic analysis to fine-tune targeted therapy: results of the Phase II LOGIC 2 trial in patients with BRAF**^V600-mutant metastatic melanoma**

During part I of the Phase II LOGIC 2 trial, patients with advanced melanoma with BRAF^V600 mutations (75 BRAF/MEK inhibitor–naïve, 83 BRAF/MEK inhibitor–pretreated) received encorafenib plus binimetinib treatment. Objective response rate (ORR) was 73.3 percent in BRAF/MEK inhibitor–naïve patients and 25.3 percent in pretreated patients. In part II, a third targeted therapy was added to the treatment regimen; ORR was 2.6 percent for those who received ribociclib triplet combination (n=38) and 0 percent for those who received capmatinib (n=13) and buparlisib (n=6) triplet combinations. Adverse events (AEs) that were suspected to be drug-related were reported in 85.4 percent of patients in part I; in part II, such AEs were reported in 84.2 percent of patients treated with ribociclib triplet regimen, 76.9 percent of those treated with capmatinib triplet regimen, and 50.0 percent of those treated with buparlisib triplet regimen.

Source: Dummer R, Sandhu S, Miller WH Jr, et al. Longitudinal genomic analysis to fine-tune targeted therapy: results of the Phase II LOGIC 2 trial in patients with BRAF^V600-mutant metastatic melanoma. Clin Cancer Res. 2025;31(11):2097–2107.