FDG-PET associations with pathological response and survival with neoadjuvant immunotherapy for melanoma.
Abstract Background: Neoadjuvant immunotherapy has become the new standard of care for stage III melanoma. This study sought to describe the metabolic changes seen with fludeoxyglucose-18-positron emission tomography (FDG-PET) following neoadjuvant immunotherapy in patients with melanoma and explore associations with pathological response and recurrence-free survival (RFS). Methods: Data from patients with macroscopic stage III nodal melanoma treated with neoadjuvant checkpoint inhibitor therapy were pooled from five melanoma centers. All patients underwent baseline and preoperative FDG-PET and CT assessments, and all had surgery. Pathological response was determined using the International Neoadjuvant Melanoma Consortium criteria, radiological response using Response Evaluation Criteria in Solid [...]
Neoadjuvant triplet immune checkpoint blockade in newly diagnosed glioblastoma.
Abstract Glioblastoma (GBM) is an aggressive primary adult brain tumor that rapidly recurs after standard-of-care treatments, including surgery, chemotherapy and radiotherapy. While immune checkpoint inhibitor therapies have transformed outcomes in many tumor types, particularly when used neoadjuvantly or as a first-line treatment, including in melanoma brain metastases, they have shown limited efficacy in patients with resected or recurrent GBM. The lack of efficacy has been attributed to the scarcity of tumor-infiltrating lymphocytes (TILs), an immunosuppressive tumor microenvironment and low tumor mutation burden typical of GBM tumors, plus exclusion of large molecules from the brain parenchyma. We hypothesized that upfront [...]
Clinical outcomes and management following progressive disease with anti-PD-(L)1 therapy in patients with advanced Merkel Cell Carcinoma.
Abstract Aim: Merkel Cell Carcinoma (MCC) is a rare skin cancer with a rising incidence worldwide. Anti-programmed death-1/ligand-1 (anti-PD-(L)1) therapies are effective for the treatment of advanced MCC. This study examines patterns of response / progression of advanced MCC to anti-PD-(L)1 therapies and describes subsequent management. Method: This is a multi-centre international retrospective cohort study with data collected up to May 2023 from 17 centres across 6 countries. Outcomes included objective response rate (ORR), duration of response (DOR), progression-free survival (PFS), and overall survival (OS) for anti-PD-(L)1 and subsequent therapy. Results: One-hundred and eighty-five advanced MCC patients received anti-PD-(L)1 therapy. At median [...]
G9a Inhibition Enhances Checkpoint Inhibitor Blockade Response in Melanoma.
Abstract Purpose: G9a histone methyltransferase exerts oncogenic effects in several tumor types and its inhibition promotes anticancer effects. However, the impact on checkpoint inhibitor blockade response and the utility of G9a or its target genes as a biomarker is poorly studied. We aimed to examine whether G9a inhibition can augment the efficacy of checkpoint inhibitor blockade and whether LC3B, a G9a target gene, can predict treatment response. Experimental design: Clinical potential of LC3B as a biomarker of checkpoint inhibitor blockade was assessed using patient samples including tumor biopsies and circulating tumor cells from liquid biopsies. Efficacy of G9a inhibition to enhance checkpoint [...]
Multiomic profiling of checkpoint inhibitor-treated melanoma: Identifying predictors of response and resistance, and markers of biological discordance.
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An updated review of immune checkpoint inhibitors in cutaneous oncology: Beyond melanoma.
Abstract Over the last decade, immune checkpoint inhibitors (ICIs) have been established as an integral component of the contemporary anticancer armamentarium. In dermatology, ICIs are most established as treatment of advanced melanoma. However, emerging evidence has demonstrated that their utility in cutaneous oncology extends to a variety of other non-melanoma malignancies. This review provides an update of the evidence from clinical trials, real world analyses, and translational research over the last three years in cutaneous malignancies beyond melanoma. Special focus is presented on areas warranting further evaluation - including populations underrepresented in or excluded from clinical trials; new and [...]
An updated review of immune checkpoint inhibitors in cutaneous oncology: Beyond melanoma.
Abstract Over the last decade, immune checkpoint inhibitors (ICIs) have been established as an integral component of the contemporary anticancer armamentarium. In dermatology, ICIs are most established as treatment of advanced melanoma. However, emerging evidence has demonstrated that their utility in cutaneous oncology extends to a variety of other non-melanoma malignancies. This review provides an update of the evidence from clinical trials, real world analyses, and translational research over the last three years in cutaneous malignancies beyond melanoma. Special focus is presented on areas warranting further evaluation - including populations underrepresented in or excluded from clinical trials; new and [...]
An updated review of immune checkpoint inhibitors in cutaneous oncology: Beyond melanoma.
Abstract Over the last decade, immune checkpoint inhibitors (ICIs) have been established as an integral component of the contemporary anticancer armamentarium. In dermatology, ICIs are most established as treatment of advanced melanoma. However, emerging evidence has demonstrated that their utility in cutaneous oncology extends to a variety of other non-melanoma malignancies. This review provides an update of the evidence from clinical trials, real world analyses, and translational research over the last three years in cutaneous malignancies beyond melanoma. Special focus is presented on areas warranting further evaluation - including populations underrepresented in or excluded from clinical trials; new and [...]
Size matters: integrating tumour volume and immune activation signatures predicts immunotherapy response.
Abstract Immune checkpoint inhibitors (ICIs) have transformed cancer treatment, providing significant benefit to patients across various tumour types, including melanoma. However, around 40% of melanoma patients do not benefit from ICI treatment, and accurately predicting ICI response remains challenging. We now describe a novel and simple approach that integrates immune-associated transcriptome signatures and tumour volume burden to better predict ICI response in melanoma patients. RNA sequencing was performed on pre-treatment (PRE) tumour specimens derived from 32 patients with advanced melanoma treated with combination PD1 and CTLA4 inhibitors. Of these 32 patients, 11 also had early during treatment (EDT, 5-15 [...]
1094P NeoRisk: Neoadjuvant immunotherapy (NeoIT) recurrence risk assessment tool
Background NeoIT with anti-PD-1 (PD1) is now a standard of care for patients (pts) with resectable stage IIIB–D melanoma. Although pathological response is predictive of recurrence, this variable alone cannot accurately identify those pts who will recur, particularly non-responders. We sought to build a recurrence risk assessment tool based on pts demographics, disease characteristics, pathological and imaging data. Methods Pts with resectable stage IIIB–D melanoma treated with PD1-based neoIT were included. Pts demographics, disease characteristics, blood parameters, pathological and imaging data at baseline (BL) and post-treatment (post-Tx), and clinical outcomes were analysed. A penalised multivariable logistic regression model was [...]