The collateral damage caused by COVID-19 pandemic-associated public health and governmental measures on patient care has been increasingly assessed in various oncological and non-oncological clinical settings. In order to investigate potential adverse effects in the field of melanoma the present study analyzed the characteristics of primary melanoma diagnoses at an Austrian dermato-pathological referral center before, during, and after the first coronavirus-related lockdown in March 2020. As suspected, we found significant temporary reductions in the number of newly diagnosed melanomas in 2020 compared to previous years, in particular, during the first lockdown period.

Background: Programmed death-1 (PD-1) antibodies and BRAF + MEK inhibitors are widely used for adjuvant therapy of fully resected high-risk melanoma. Little is known about treatment efficacy outside of phase III trials. This real-world study reports on clinical outcomes of modern adjuvant melanoma treatment in specialized skin cancer centers in Germany, Austria and Switzerland. Methods: Multicenter, retrospective study investigating stage III-IV melanoma patients receiving adjuvant nivolumab (NIV), pembrolizumab (PEM) or dabrafenib + trametinib (D + T) between 1/2017 and 10/2021. The primary endpoint was 12-month recurrence-free survival (RFS). Further analyses included descriptive and correlative statistics, and a multivariate linear-regression machine learning model to assess the risk of early melanoma recurrence. Results: In total, 1198 patients from 39 skin cancer centers from Germany, Austria and Switzerland were analysed. The vast majority received anti PD-1 therapies (n = 1003). Twelve-month RFS for anti PD-1 and BRAF + MEK inhibitor-treated patients were 78.1% and 86.5%, respectively (hazard ratio [HR] 1.998 [95% CI 1.335-2.991]; p = 0.001). There was no statistically significant difference in overall survival (OS) in anti PD-1 (95.8%) and BRAF + MEK inhibitor (96.9%) treated patients (p > 0.05) during the median follow-up of 17 months. Data indicates that anti PD-1 treated patients who develop immune-related adverse events (irAEs) have lower recurrence rates compared to patients with no irAEs (HR 0.578 [95% CI 0.443-0.754], p = 0.001). BRAF mutation status did not affect overall efficacy of anti PD-1 treatment (p > 0.05). In both, anti PD-1 and BRAF + MEK inhibitor treated cohorts, data did not show any difference in 12-month RFS and 12-month OS comparing patients receiving total lymph node dissection (TLND) versus sentinel lymph node biopsy only (p > 0.05). The recurrence prediction model reached high specificity but only low sensitivity with an AUC = 0.65. No new safety signals were detected. Overall, recorded numbers and severity of adverse events were lower than reported in pivotal phase III trials. Conclusions: Despite recent advances in adjuvant melanoma treatment, early recurrence remains a significant clinical challenge. This study shows that TLND does not reduce the risk of early melanoma recurrence and should only be considered in selected patients. Data further highlight that variables collected during clinical routine are unlikely to allow for a clinically relevant prediction of individual recurrence risk.

Summary Background Anti‐programmed death 1 (PD‐1) antibodies have evolved as a new standard of care in the adjuvant treatment of completely resected melanoma. Real‐world data on treatment efficacy and safety as well as cost‐effectiveness are still limited. Patients and Methods Treatment outcomes were retrospectively analyzed in a continuous patient cohort receiving adjuvant nivolumab (91 patients) or pembrolizumab (9 patients). Based on the obtained clinical data, a semi‐Markov model was developed to evaluate cost‐effectiveness. Results After a median follow‐up of 11.5 months, disease recurrence was observed in 39 patients (39 %). The site of first recurrence was locoregional in 17, distant in 19, and combined locoregional and distant in three patients. Twelve‐month estimates for recurrence‐ and distant‐metastasis‐free survival were 64.8 % and 77.4 %, respectively. Sixteen patients experienced grade 3 or 4 treatment‐related adverse events, while 22 patients discontinued treatment due to adverse events. The base‐case Markov model yielded an incremental cost‐effectiveness ratio of 13,330 € per quality‐adjusted life year for adjuvant anti‐PD‐1 antibody treatment compared to a simulated observation cohort. Conclusions Real‐world outcomes of adjuvant anti‐PD‐1 antibody therapy in completely resected melanoma appear comparable to clinical trial data. Moreover, our data suggests this treatment strategy to be cost‐effective according to Austrian health economic standards.

Background The COVID‐19 lockdown had a dramatic impact on primary care access and resulted in postponed skin cancer screenings. This raises concerns for a diagnostic delay on primary cutaneous melanomas, which can subsequently increase morbidity and mortality. Objectives The aim of the study was to investigate the impact of the COVID‐19‐related restrictions on the melanoma diagnosis in five European skin cancer reference centres in Switzerland, Germany, Austria and Italy. Methods A total of 7865 cutaneous melanoma cases were collected between 01 September 2018 and 31 August 2021. The time period was stratified into pre‐COVID (pre‐lockdown) and post‐COVID (lockdown and post‐lockdown) according to the established restrictions in each country. The data collection included demographic, clinical and histopathological data from histologically confirmed cutaneous melanomas. Personal and family history of melanoma, and presence of immunosuppression were used to assess the diagnosis delay in high‐risk individuals. Results There was an overall increase of the Breslow tumour thickness (mean 1.25 mm vs. 1.02 mm) during the post‐COVID period, as well as an increase in the proportion of T3‐T4 melanomas, rates of ulceration and the number of mitotic rates ≥2 (all, p < 0.001). Patients with immunosuppression and personal history of melanoma showed a decrease in the mean log10‐transformed Breslow during lockdown and post‐COVID. In the multivariate analysis, age at melanoma diagnosis (p < 0.01) and personal history of melanoma (p < 0.01) showed significant differences in the mean Breslow thickness. Conclusions The study confirms the diagnostic delay in cutaneous melanomas due to the COVID‐19 lockdown. High‐risk individuals, such as patients with personal history of melanoma and elderly individuals, were more hesitant to restart their regular skin cancer screenings post‐COVID. Further studies with longer follow‐up are required to evaluate the consequences of this diagnostic delay in long‐term outcomes.

CXCL13 is a potent chemoattractant cytokine that promotes the migration of cells expressing its cognate receptor, CXCR5. Accordingly, T follicular helper cells and B cells migrate towards B cell follicles in lymph nodes, where the resulting spatial proximity promotes B cell/T cell interaction and antibody formation. Moreover, effector cells of the CXCL13/CXCR5-associated immune axis express PD-1, with corresponding circulating cells occurring in the blood. The formation of so-called ectopic or tertiary lymphoid structures, recently detected in different cancer types, represents an integral part of this axis, particularly in the context of its emerging role in anti-tumor defense. These aspects of the CXCL13/CXCR5-associated immune axis are highlighted in this review, which focuses on cutaneous malignant melanoma. Specifically, we elaborate on the role of this important immune axis as a possible ancillary target of immune checkpoint inhibition with anti-PD-1 antibodies in different therapeutic settings and as a potential source of predictive biomarkers regarding treatment efficacy.