Journal of Clinical and Aesthetic Dermatology • Hot Topics in Melanoma July 2025 • MEETING HIGHLIGHTS

The American Society of Clinical Oncology held its 2025 Annual Meeting from May 30 to June 3, 2025, in Chicago, Illinois. The conference gave researchers, physicians, and members of industry the opportunity to share and learn about the latest research in cutaneous oncology, including melanoma. The event included speaker presentations on various clinical topics in melanoma, as well as posters reporting the latest data on melanoma screening, biomarkers, and treatment options. Summaries of key abstracts from the meeting are included here.

The 31-gene expression profile as a guide to better risk-aligned care decisions for patients with Stage I–III cutaneous melanoma: an NCI-SEER analysis. This retrospective study evaluated the prognostic utility of the 31-gene expression profile (31-GEP) in stratifying mortality risk among 13,560 patients with Stage I to III cutaneous melanoma (CM) using linked Surveillance, Epidemiology, and End Results (SEER) registry data from 2013 to 2019. Five-year melanoma-specific survival (MSS) rates were significantly higher in patients with a Class 1A 31-GEP result compared to those with Class 1B/2A or Class 2B results (99.1% vs. 92.5% and 85.9%, respectively; p<0.001). Multivariable analysis identified a Class 2B result (hazard ratio [HR]: 4.20, p<0.001) and Class 1B/2A result (HR: 3.21, p<0.001), as well as lymph node positivity, Breslow thickness, ulceration, age, and mitotic rate, as significant predictors of melanoma-specific mortality (MSM). Subgroup analyses across disease stages revealed consistently higher MSS among patients with a Class 1A result, compared to those with Class 1B/2A or 2B results. Additionally, 31-GEP-tested patients demonstrated a lower risk of MSM compared to untested, propensity score–matched patients (HR=0.68, p<0.001). These findings suggest that the 31-GEP test independently stratifies mortality risk across staging groups and could support more individualized treatment and management strategies for patients with CM.

Long-term outcomes following melanoma metastasectomy categorized by response to immune checkpoint inhibitor (ICI) therapy. In a cohort of 513 patients with Stage III/IV melanoma undergoing surgery after immune checkpoint inhibitor (ICI) therapy, 83 percent had Stage IV disease and 17 percent had Stage III disease at therapy initiation. Patients were categorized as having stable/responding disease (R; n=76), isolated progression (IP; n=227), or multiple progressing sites (MP; n=210). Median disease-specific survival (DSS) following surgery was 4.1 years (95% confidence interval [CI]: 2.5–not reached [NR]), with resection to no evidence of disease (NED) at first operation achieved in 39 percent of patients, which was associated with significantly improved five-year DSS (81% vs. 26%; p<0.001). Five-year DSS rates were 89 percent for R tumors and 62 percent for IP tumors, compared to 20 percent for MP tumors (p<0.001). Resection to NED and pathologic complete response (pCR) were identified as independent predictors of DSS, supporting surgery’s role in select patients while highlighting the need for alternative therapeutic strategies for those with MP tumors.

Homologous recombination deficiency signature (HRDsig) in advanced cutaneous melanoma (ACM): a genomic landscape study. In an analysis using comprehensive genomic profiling (CGP) of formalin-fixed paraffin-embedded (FFPE) primary tumors and metastatic biopsies from 9,576 advanced CM (ACM) cases, 2.1 percent were positive for homologous recombination deficiency signature (HRDsig+). Compared to HRDsig-negative (HRDsig–) cases, HRDsig+ tumors were associated with older median age (69 vs. 67 years; p=0.034), female sex (49.5% vs. 36.2%; p=0.001), and higher number of genomic alterations per tumor (median: 7 vs. 6; p=0.026). HRDsig+ tumors exhibited higher frequencies of IGF1R, KIT, KRAS, NF1, RAD21, and TP53 alterations, while HRDsig– tumors had higher tumor mutational burden (TMB), more ultraviolet light exposure trinucleotide signatures, and more frequent BRAF, CDKN2A, NRAS, and TERT alterations. BRCA1/2 alterations were similarly low across both groups. Additionally, the rate of programmed death-ligand 1 (PD-L1) tumor proportion score (TPS) of 1 to 49 percent was similar across groups. These findings suggest that HRDsig+ status, though rare, may inform future clinical trial designs involving combination therapies and guide poly(ADP-ribose) polymerase inhibitor use in ACM.

Demographic and clinical disparities in early mortality of patients with metastatic melanoma: a SEER-based analysis (2000–2021). Using SEER data from 2000 to 2021, this study analyzed early mortality, defined as survival of less than six months, in 487 patients with metastatic melanoma. Median overall survival (OS) was 2.9 months, with younger patients (<65 years of age) showing longer survival than older patients (≥65 years of age; 3.2 vs. 2.8 months; p<0.001). Female patients had longer median survival than male patients (3.1 vs. 2.7 months; p=0.008), and Hispanic patients had the highest three-month survival probability (30.2%) compared to other racial/ethnic groups. The risk of mortality was lower in younger patients compared to their older counterparts (HR: 2.31 vs. 3.02, p<0.001). Beam radiation was associated with modestly improved survival, compared to no radiation therapy (3.0 vs. 2.6 months; p=0.012). Melanoma of the trunk conferred the highest three-month survival probability (30.8%), while melanoma localized to the scalp and neck region had the lowest probability (25.7%). Disparities in early mortality were observed across age, gender, race, and treatment modalities, underscoring the need for targeted interventions.

Long-term follow-up of patterns of melanoma early and late recurrence after adjuvant anti-PD1 therapy. Understanding the recurrence patterns of melanoma is important to help develop interventions to improve patient outcomes. In a prospective study of 172 ICI-naïve patients with resected high-risk melanoma treated with adjuvant anti-programmed cell death-1 (PD-1) therapy, 52 percent experienced recurrence over a median follow-up of 36 months. Among those with disease recurrence, 66 percent had early progressive disease (PD) and 34 percent had late PD. Among the 24 patients with resectable recurrence, the subsequent PD rate after surgery was 36 percent with adjuvant anti-PD-1 therapy, 57 percent with adjuvant ipilimumab/ nivolumab, and 100 percent with adjuvant targeted therapy. Adjuvant targeted therapy was associated with a shorter median time to next treatment (TTNT). Systemic therapy outcomes post-recurrence varied, with objective response rates (ORRs) of 57 percent for anti-PD-1 therapy rechallenge and 62 percent for targeted therapy with or without anti-PD-1 therapy. Patients who benefited from systemic ICI treatment were likely to have higher median TMB, while patients with lower median TMB showed treatment benefit with talimogene laherparepvec–based approaches.

Clinical and biomarker analyses of first-line nivolumab and relatlimab (nivo-rela) in advanced or resectable melanoma. In a study of 128 patients with melanoma treated with first-line nivolumab and relatlimab, 101 were treated in the advanced setting and 27 in the neoadjuvant setting. In the advanced cohort, median progression-free survival (PFS) was 19 months (95% CI: 10–NR), and median OS was not reached after a median follow-up of 13 months. Among evaluable neoadjuvant patients, the major pathologic response rate was 48 percent, with complete responses reported in 29 percent of patients. Adverse events (AEs) included adrenal insufficiency and myocarditis. Tumor microenvironment analysis showed no significant differences in lymphocyte activation gene-3 (LAG-3), PD-1, PD-L1, or CD8+ expression between responders and nonresponders. However, nonresponders exhibited high B7-H3 expression at baseline. CD163+, CD68+, CD14+, and fibroblast activation protein alpha were enriched in B7-H3 regions of interest. These findings suggest that B7-H3 expression may contribute to nonresponse to nivolumab and relatlimab combination therapy and support further investigation of B7-H3-targeted therapies.

Anxiety, depression, fear of cancer recurrence (FCR) and health-related quality of life (HRQoL) in people with melanoma receiving adjuvant therapies. In a prospective, longitudinal study of 52 patients with resected Stage IIB to IV melanoma receiving adjuvant anti-PD-1 or dabrafenib-trametinib, emotional distress was assessed up to two years post-treatment initiation. Mild-to-severe anxiety, depression, and clinically significant fear of cancer recurrence (FCR) were prevalent during follow-up. Patients with anxiety or depression at 24 months reported worse HRQoL, with mean Functional Assessment of Cancer Therapy-General (FACT-G) scores of 67.8 and 69.7, respectively, compared to 82.8 and 84.2 in those without such symptoms. All patients with clinically significant FCR at 12 months continued to report FCR at 24 months, and those with FCR at 24 months had worse HRQoL compared to patients without clinically significant FCR (mean FACT-G score: 67.7 vs. 80.5). These findings highlight the need for psychological screening to help identify patients who would benefit from targeted interventions.

Sensitivity of circulating tumor DNA (ctDNA) for disease recurrence or relapse in patients with melanoma. In a retrospective cohort study of 116 patients with melanoma monitored with a personalized, tumor-informed circulating tumor deoxyribonucleic acid (ctDNA) assay, 48 percent experienced confirmed recurrence or relapse. In 53.6 percent of these cases, ctDNA was detected, with sensitivity varying by site of recurrence; sensitivity was highest for liver and lymph node metastases (both 87.5%), followed by bone (75%), lung (61.5%), skin/mucosa/muscle (37.5%), and brain (33.3%) metastases. Logistic regression analysis showed significantly higher odds of ctDNA detection in patients with lymph node metastases (odds ratio [OR]: 10.5; p=0.004) and those with multiple metastatic sites (OR: 7.61; p=0.032). These findings suggest that the anatomic location of metastases influences ctDNA shedding and detection rates. Further large-scale studies are warranted to refine ctDNA’s role in melanoma surveillance.

Clinical and radiometabolic correlatives of ddPCR liquid biopsy for BRAF**^V600 mutated melanoma.** In a study of 71 patients with BRAF^V600-mutant melanoma, 65 percent had a positive droplet digital polymerase chain reaction (ddPCR) test result for ctDNA, using a cutoff of four or more mutant copies/mL. Patients with positive tests were younger (p=0.047), had more osseous metastases (p=0.02), and had a higher number of lesions (p=0.006). Total tumor volume on positron emission tomography/computed tomography (PET/CT) was predictive of ctDNA levels, with every 10mL increase in tumor volume associated with an increase of 370 copies/mL in ddPCR (p<0.001). Logistic regression showed that presence of six or more lesions (OR: 6.57) and elevated lactate dehydrogenase (OR: 8.8) were associated with an increased risk of a positive ddPCR result, while younger age was linked to a decreased risk of a positive result (OR: 0.92). These findings suggest that ddPCR-based liquid biopsy correlates with disease burden and can be used to assess patients with high tumor disease states.

Real-world outcomes in patients with brain metastases secondary to melanoma treated with nivolumab/relatlimab. This retrospective cohort study evaluated the clinical activity of nivolumab and relatlimab in 44 patients with melanoma brain metastases (MBM). Median follow-up was 25 months. The median interval from MBM diagnosis to nivolumab and relatlimab initiation was 8.6 months, with only 13.6 percent receiving the combination in the first-line setting. At treatment initiation, 39 patients had brain metastases, most with 1 to 3 lesions (68.2%), and 75.0 percent received local intracranial stereotactic radiotherapy. The estimated OS rates at one and two years following MBM diagnosis were 77 percent (95% CI: 62–87%) and 67 percent (95% CI: 50–80%), respectively. Intracranial clinical benefit, defined as stable or decreasing brain lesion size, was observed in 45.5 percent of patients, and durable extracranial clinical benefit (stable disease, partial response, or complete response sustained for 6 months) occurred in 38.6 percent of patients. These findings suggest that nivolumab and relatlimab might have intracranial activity in patients with MBM, particularly when used earlier in the treatment course.

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

Fifty-five percent of patients with melanoma who developed immune checkpoint inhibitor (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.

Source: Lin W, Wang W, Hodi FS, Min L. Gaps in the management of adrenal insufficiency in melanoma survivors: a retrospective cohort study. EClinicalMedicine. 2024;79:102984.

RESEARCH BITE—The effect of concomitant immunotherapy and stereotactic radiotherapy and of location on survival in patients with brain metastases from melanoma

This retrospective study of 92 patients with melanoma brain metastases evaluated the impact of brain metastasis location and concomitant stereotactic radiotherapy (SRT) with immunotherapy (IRT) on clinical outcomes. The median overall survival (OS) was 9.8 months, with no significant OS differences observed across treatment regimens in a subgroup of 56 patients. However, patients with both infra- and supratentorial brain metastases had significantly reduced OS compared to those with only supratentorial lesions (hazard ratio [HR]: 2.81; p<0.01), and location was identified as an independent prognostic factor. The use of IRT was associated with a significant improvement in intracranial progression-free survival (HR: 0.32; p=0.01). These findings suggest that while OS might not differ by treatment modality overall, the addition of SRT to immunotherapy might improve intracranial disease control, and the presence of both infra- and supratentorial metastases is linked to poorer survival outcomes.

Source: Nijboer CB, Piersma D, Sijben AEJ, et al. The effect of concomitant immunotherapy and stereotactic radiotherapy, and of location on survival in patients with brain metastases from melanoma. Cancer Med. 2025;14(11):e70923.