Adjuvant anti-PD-1 therapy improves melanoma-specific survival in stage IIIC-IV melanoma patients with high tumor mutation burden and mutation.

Immune checkpoint inhibitors (ICI) have significantly improved melanoma-specific survival (MSS), particularly in patients with tumors with a high tumor mutational burden (TMB) or mutation. In the adjuvant setting, ICIs significantly improve relapse-free survival (RFS), but data on MSS are still lacking. Tissue samples from 83 patients with stage IIIC/D/IV melanoma who started adjuvant ICI between March 2018 and September 2019 were examined using a 700 gene panel.

Adjuvant Cemiplimab or Placebo in High-Risk Cutaneous Squamous-Cell Carcinoma.

Background: Patients who have cutaneous squamous-cell carcinoma with high-risk features are at risk for recurrence after definitive local therapy. The benefit of systemic adjuvant therapy options has not been well established in clinical trials.

Methods: In a phase 3, randomized trial, we enrolled patients with local or regional cutaneous squamous-cell carcinoma, after surgical resection and postoperative radiotherapy, at high risk for recurrence owing to nodal features (extracapsular extension with largest node ≥20 mm in diameter or at least three involved nodes) or nonnodal features (in-transit metastases, T4 lesion [with bone invasion], perineural invasion, or locally recurrent tumor with ≥1 additional risk feature).

Psychosocial distress and persistent adverse events in long-term survivors of stage IV melanoma - a cross-sectional questionnaire study.

Background: Immune checkpoint inhibitors and targeted therapies have improved survival in patients with stage IV melanoma. However, the challenges faced by long-term survivors remain unclear. The long-term toxicity and psychosocial impact of these treatments in real-world patients have yet to be reported.

Risk stratification using the Merlin Assay (CP-GEP) in an independent cohort of 930 patients with clinical stage I/II melanoma who did not undergo sentinel lymph node biopsy.

Purpose: More than 80 % of patients with melanoma are diagnosed without nodal metastasis, but most of those who relapse or die from melanoma are initially diagnosed as low risk early-stage. Here we investigate the ability of the Merlin Assay to stratify patients who did not undergo sentinel lymph node biopsy (SLNB) for their risk of recurrence.

Patients And Methods: 930 patients with clinical stage I/II primary cutaneous melanoma from the University of Tuebingen diagnosed between 2000 and 2020 were analyzed.

Open-label nonrandomized phase IB study to characterize the safety and recommended dose of tinostamustine in combination with nivolumab in patients with advanced melanoma (ENIgMA).

Tinostamustine is a first-in-class alkylating deacetylase inhibitor that facilitates access to cancer cell DNA, resulting in its damage and counteracting DNA repair systems. We hypothesize that the addition of tinostamustine to immune checkpoint inhibitors (ICIs) improves melanoma treatment. This open-label, nonrandomized phase IB study characterized dose-limiting toxicity (DLT) and the recommended dose (RD) of 2-weekly intravenous tinostamustine at escalating doses of 15 and 30 mg/m 2 when administered with 2-weekly nivolumab 3 mg/kg added in cycle 2 in patients with melanoma.

Comparative real-world outcomes of stage III melanoma patients treated with talimogene laherparepvec or interleukin 2.

Background: Talimogene laherparepvec (T-VEC) and interleukin-2 (IL-2) are both used in the intralesional treatment of melanoma skin metastases. T-VEC received regulatory approval from the European Medicines Agency and the U.S.

Discontinuation of immune checkpoint inhibitors for reasons other than disease progression and the impact on relapse and survival of advanced melanoma patients. A systematic review and meta-analysis.

Background: Despite durable responses achieved with Immune Checkpoint Inhibitors (ICIs), data about optimal duration of treatment, especially in the context of adverse events, remain scarce.

Objective: To systematically review the evidence concerning the impact of treatment discontinuation with ICIs for reasons other than progressive disease (PD) on relapse rates and survival of melanoma patients.

Methods: A systematic literature search was conducted in three electronic databases until July 2024.

A comparison of real-world data on adjuvant treatment in patients with stage III BRAF V600 mutated melanoma - Results of systematic literature research.

Background: Over the past decade, PD-1-based immune checkpoint inhibitors (ICI) and targeted therapies (TT) with BRAF and MEK inhibitors transformed melanoma treatment. Both are widely used in the adjuvant setting. However, for patients with a BRAF V600 mutation, the optimal adjuvant therapy remains unclear due to the lack of head-to-head comparison studies.

Multimodal Profiling of Peripheral Blood Identifies Proliferating Circulating Effector CD4 T Cells as Predictors for Response to Integrin α4β7-Blocking Therapy in Inflammatory Bowel Disease.

Background & Aims: Despite the success of biological therapies in treating inflammatory bowel disease, managing patients remains challenging due to the absence of reliable predictors of therapy response.

Methods: In this study, we prospectively sampled 2 cohorts of patients with inflammatory bowel disease receiving the anti-integrin α4β7 antibody vedolizumab. Samples were subjected to mass cytometry; single-cell RNA sequencing; single-cell B and T cell receptor sequencing (BCR/TCR-seq); serum proteomics; and multiparametric flow cytometry to comprehensively assess vedolizumab-induced immunologic changes in the peripheral blood and their potential associations with treatment response.

Melanoma-specific survival of patients with uveal melanoma and liver metastases diagnosed between 2005 and 2021.

Background: Uveal melanoma is the most common malignant tumor of the eye in adults. About half of the patients develop distant metastases, most commonly liver metastases (>90%). These are associated with poorer overall survival compared to patients with extrahepatic metastases.

An Automated Real-Time PCR Assay versus Next-Generation Sequencing in the Detection of V600 Mutations in Melanoma Tissue Samples.

Background: Next-generation sequencing (NGS) is the most commonly used method for determining mutational status in patients with advanced melanoma. Automated PCR-based methods, such as the Idylla system, are increasingly used for mutation diagnostics, but it is unclear what impact the choice of diagnostic method has on the management of melanoma.

Objectives: To compare the concordance rate of V600 mutational analysis using Idylla and NGS and to analyze the technical and clinical turnaround time.

Response and outcome of patients with melanoma skin metastases and immune checkpoint inhibition.

It is known, that different metastatic organ systems respond differently to immune checkpoint inhibitors (ICIs). In this study, we aimed to investigate the extent to which skin/subcutaneous metastases respond to ICI or targeted therapies (TTs) and whether the response rate differs from that of distant metastases in the same patient. Patients with melanoma diagnosed between January 2021 and September 2023 with at least one skin/subcutaneous metastasis who had received therapy with ICI or TT in an advanced setting were included in the analysis.

Expression of the tumor antigens NY-ESO-1, tyrosinase, MAGE-A3, and TPTE in pediatric and adult melanoma: a retrospective case control study.

Tumor-associated antigens (TAAs) are potential targets for T cell-based immunotherapy approaches in cutaneous melanoma. BNT111, an investigational lipoplex-formulated mRNA-based therapeutic cancer vaccine encoding melanoma TAAs NY-ESO-1, tyrosinase, MAGE-A3, and TPTE, is undergoing clinical testing in adults. Expression of these TAAs in pediatric melanoma is unclear but is a prerequisite for feasibility of this treatment approach in children with melanoma.

Neuropathological assessment of the olfactory bulb and tract in individuals with COVID-19.

The majority of patients with Parkinson disease (PD) experience a loss in their sense of smell and accumulate insoluble α-synuclein aggregates in their olfactory bulbs (OB). Subjects affected by a SARS-CoV-2-linked illness (COVID-19) also frequently experience hyposmia. We previously postulated that microglial activation as well as α-synuclein and tau misprocessing can occur during host responses following microbial encounters.

Autoimmunity Against Surfactant Protein B Is Associated with Pneumonitis During Checkpoint Blockade.

Immune checkpoint inhibitor (ICI)-related pneumonitis is a serious autoimmune event affecting as many as 20% of patients with non-small-cell lung cancer (NSCLC), yet the factors underpinning its development in some patients and not others are poorly understood. To investigate the role of autoantibodies and autoreactive T cells against surfactant-related proteins in the development of pneumonitis. The study cohort consisted of patients with NSCLC who provided blood samples before and during ICI treatment.

Isolated melanoma cells in sentinel lymph node in stage IIIA melanoma correlate with a favorable prognosis similar to stage IB.

Background: The American Joint Committee on Cancer 8th edition (AJCC v8) defines sentinel lymph nodes (SLN) containing any tumor cells as positive SLN. Consequently, even thin melanomas with isolated tumor cells (ic) in SLN are classified as stage IIIA, making them candidates for adjuvant therapy.

Objectives And Endpoints: We aimed to evaluate survival outcomes of melanoma stage IIIA (ic) and compare them with stage IIIA with lymph node (LN) metastases > 0.

Augmenting MEK inhibitor efficacy in BRAF wild-type melanoma: synergistic effects of disulfiram combination therapy.

Background: MEK inhibitors (MEKi) were shown to be clinically insufficiently effective in patients suffering from BRAF wild-type (BRAF WT) melanoma, even if the MAPK pathway was constitutively activated due to mutations in NRAS or NF-1. Thus, novel combinations are needed to increase the efficacy and duration of response to MEKi in BRAF WT melanoma. Disulfiram and its metabolite diethyldithiocarbamate are known to have antitumor effects related to cellular stress, and induction of endoplasmic reticulum (ER) stress was found to synergize with MEK inhibitors in NRAS-mutated melanoma cells.

Long-term survival of stage IV melanoma patients: evaluation on 640 melanoma patients entering stage IV between 2014 and 2017.

Purpose: Since the introduction of immune checkpoint inhibitors (ICI) and targeted therapies (TT), survival rates of metastatic melanoma patients have increased significantly and complete remissions are no longer rarities. Consequently, there is an increasing number of long-term survivors who have not yet been comprehensively characterized.

Methods: We included melanoma patients who entered stage IV between 2014 and 2017 and survived at least 5 years after entering stage IV.

Acidosis-mediated increase in IFN-γ-induced PD-L1 expression on cancer cells as an immune escape mechanism in solid tumors.

Immune checkpoint inhibitors have revolutionized cancer therapy, yet the efficacy of these treatments is often limited by the heterogeneous and hypoxic tumor microenvironment (TME) of solid tumors. In the TME, programmed death-ligand 1 (PD-L1) expression on cancer cells is mainly regulated by Interferon-gamma (IFN-γ), which induces T cell exhaustion and enables tumor immune evasion. In this study, we demonstrate that acidosis, a common characteristic of solid tumors, significantly increases IFN-γ-induced PD-L1 expression on aggressive cancer cells, thus promoting immune escape.