CMV serostatus is associated with improved survival and delayed toxicity onset following anti-PD-1 checkpoint blockade.

Cytomegalovirus (CMV) is a globally endemic latent herpes virus that profoundly impacts T cell immunity. We investigated the oncological consequences of CMV infection across 341 prospectively recruited patients receiving immune checkpoint blockade (ICB) for melanoma. CMV patients with metastatic melanoma (MM) have higher lymphocyte counts, reduced neutrophil to lymphocyte ratio and divergent CD8 T cell gene expression.

Severe acute myositis and myocarditis on initiation of 6-weekly pembrolizumab post-COVID-19 mRNA vaccination.

We describe three cases of critical acute myositis with myocarditis occurring within 22 days of each other at a single institution, all within 1 month of receiving the initial cycle of the anti-PD-1 drug pembrolizumab. Analysis of T cell receptor repertoires from peripheral blood and tissues revealed a high degree of clonal expansion and public clones between cases, with several T cell clones expanded within the skeletal muscle putatively recognizing viral epitopes. All patients had recently received a COVID-19 mRNA booster vaccine prior to treatment and were positive for SARS-CoV2 Spike antibody.

A randomised phase 2 study of intermittent versus continuous dosing of dabrafenib plus trametinib in patients with BRAF mutant advanced melanoma (INTERIM).

Background: BRAF+MEK inhibitors extend life expectancy of patients with BRAF mutant advanced melanoma. Acquired resistance limits duration of benefit, but preclinical and case studies suggest intermittent dosing could overcome this limitation. INTERIM was a phase 2 trial evaluating an intermittent dosing regimen.

IL7 genetic variation and toxicity to immune checkpoint blockade in patients with melanoma.

Treatment with immune checkpoint blockade (ICB) frequently triggers immune-related adverse events (irAEs), causing considerable morbidity. In 214 patients receiving ICB for melanoma, we observed increased severe irAE risk in minor allele carriers of rs16906115, intronic to IL7. We found that rs16906115 forms a B cell-specific expression quantitative trait locus (eQTL) to IL7 in patients.

Delphi panel for consensus on the optimal management of dabrafenib plus trametinib-related pyrexia in patients with melanoma.

Purpose: Dabrafenib and trametinib combination therapy (dab + tram) is indicated to treat BRAF V600 mutation-positive unresectable/metastatic melanoma and as adjuvant treatment for resected stage III disease. Dab + tram-related pyrexia may require early therapy discontinuation. A modified Delphi panel was conducted to develop consensus on the optimal management of dab + tram-related pyrexia in patients with melanoma.

Association Between a Distinctive Autoantibody-Associated Brainstem Sensory Syndrome and Immune Checkpoint Inhibitors.

This case series investigates the association of a segmental, facial, antibody-associated brainstem sensory syndrome with the immune checkpoint inhibitor pembrolizumab.

Implications of systemic adjuvant melanoma treatments for U.K. melanoma services: Results of the U.K. Melanoma Adjuvant Pathway Survey.

Objective: To understand current U.K. management pathways for patients with resected stage III melanoma and changes expected with the routine availability of systemic adjuvant melanoma treatments.

What is the role of the surgeon in the management of head and neck mucosal melanoma in the immunotherapy era?

Introduction: The advent of immunotherapy has impacted both the management and, to a lesser extent, the outcomes for patients with head and neck mucosal melanoma. As a consequence, one might expect that the role of the surgeon would be limited to the diagnostic work-up and that systemic therapies would be the mainstay of treatment.

Methods And Results: Here, we present the surgical aspects of the recently published United Kingdom Head and Neck Mucosal Melanoma Guideline to highlight the continued role of surgeons in the management of this disease.

Impact of age on the toxicity of immune checkpoint inhibition.

Indications for immune checkpoint inhibitor therapy are increasing. As the population ages, many patients receiving such drugs will be older adults. Such patients are under-represented in clinical trials, and therefore the safety of immune checkpoint inhibitors in this population has not been adequately assessed.

Head and neck mucosal melanoma: The United Kingdom national guidelines.

The United Kingdom head and neck mucosal melanoma guideline development group used an evidence-based systematic approach to make recommendations in key areas of uncertainty in the field, including accurate diagnosis and staging; the appropriate treatment pathway including surgery, adjuvant radiation and new systemic treatments, such as targeted agents and immunotherapy; and the surveillance of patients after treatment. The guidelines were sent for international peer review and have been accredited by the National Institute for Health and Care Excellence. A summary of key recommendations is presented.

Less is more: A systematic review and meta-analysis of the outcomes of radical versus conservative primary resection in anorectal melanoma.

Introduction: Anorectal melanoma (ARM) is a rare disease with a poor prognosis. There is no consensus as to the optimal primary surgical treatment for ARM, with advocates for both radical (abdominoperineal resection [APR]) and conservative strategies (wide local excision [WLE]). Here, we report a systematic review of studies comparing outcomes between these strategies.

Ano-uro-genital mucosal melanoma UK national guidelines.

Ano-uro-genital (AUG) mucosal melanomas are rare cancers associated with poor outcomes and limited evidence-based management. The United Kingdom AUG mucosal melanoma guideline development group used an evidence-based systematic approach to make recommendations regarding the diagnosis, treatment and surveillance of patients diagnosed with AUG mucosal melanomas. The guidelines were sent for international peer review, and are accredited by The National Institute for Health and Clinical Excellence (NICE).

Immune checkpoint inhibitor-related colitis assessment and prognosis: can IBD scoring point the way?

Background: Immune checkpoint inhibitors (ICI) improve survival but cause immune-related adverse events (irAE). We sought to determine if CTCAE classification, IBD biomarkers/endoscopic/histological scores correlate with irAE colitis outcomes.

Methods: A dual-centre retrospective study was performed on patients receiving ICI for melanoma, NSCLC or urothelial cancer from 2012 to 2018.

Toxicities associated with checkpoint inhibitors-an overview.

Immunotherapy has an increasing role in the management of cancer, both in metastatic disease and as an adjuvant therapy. However, sensitization of the immune system with checkpoint inhibitors comes with a unique side effect profile. Full appreciation of this can take some time to emerge as some adverse events are rare, or can be subtle and potentially overlooked.

Immunotherapy-related hepatitis: real-world experience from a tertiary centre.

Objective: Immune checkpoint inhibitors like anti-programmed cell death protein 1 (PD-1) drugs Nivolumab and Pembrolizumab and anti-cytotoxic T-lymphocyte associated (CTLA-4) drug Ipilimumab have become standard of care in many metastatic cancers. Immunotherapy-related hepatitis and cholangitis present a diagnostic and management challenge, being rare and incompletely characterised. We aim to report the incidence, features and treatments used for this in a real-world setting and to identify useful biomarkers, which can be used to predict effective use of steroids.

Combatting mucosal melanoma: recent advances and future perspectives.

Mucosal melanomas are a rare subtype of melanoma and are associated with a particularly poor prognosis. Due to the rarity of the diagnosis, and the pace with which the management of cutaneous melanoma has evolved over recent years, there is little good evidence to guide management and evidence-based clinical guidelines are still in development in the UK. In this review we provide an overview of the management of mucosal melanoma, highlighting the critical differences between cutaneous and mucosal melanomas, before examining recent advances in the systemic treatment of this disease and likely future directions.

The impact of patient characteristics and disease-specific factors on first-line treatment decisions for BRAF-mutated melanoma: results from a European expert panel study.

Treatment decisions for advanced melanoma are increasingly complex and guidelines provide limited advice on how to choose between immunotherapy and targeted therapy for first-line treatment. A Delphi study was carried out to understand which patient characteristics and disease-related factors inform clinicians' choices of first-line treatment for BRAF-mutated melanoma. Twelve European melanoma specialists experienced in using immunotherapies and targeted agents participated in a double-blind two-phase Delphi study.

Talimogene Laherparepvec for Treating Metastatic Melanoma: An Evidence Review Group Perspective of a NICE Single Technology Appraisal.

The National Institute for Health and Care Excellence (NICE) invited the manufacturer (Amgen) of talimogene laherparepvec (T-VEC) to submit clinical and cost-effectiveness evidence for previously untreated advanced (unresectable or metastatic) melanoma as part of the Institute's Single Technology Appraisal process. The Liverpool Reviews and Implementation Group (LRiG) at the University of Liverpool was commissioned to act as the Evidence Review Group (ERG). This article presents a summary of the company's submission of T-VEC, the ERG review and the resulting NICE guidance (TA410), issued in September 2016.

Intravenous high-dose interferon with or without maintenance treatment in melanoma at high risk of recurrence: meta-analysis of three trials.

Resected stage IIB-IIIC malignant melanoma has a poor prognosis with a high risk of relapse and death. Treatment with adjuvant interferon alfa-2b (IFN-α-2b) is associated with improved relapse-free and overall survivals (OS), but the most appropriate dose and duration of treatment are unknown. In this article, we present an individual patient data random effects meta-analysis of melanoma patients from the U.