Immune Checkpoint Inhibitors for Patients With Preexisting Autoimmune Neurologic Disorders.
Abstract Importance: Immune checkpoint inhibitors (ICIs) are efficacious in many cancer types but can produce immune-related adverse events (irAEs). As such, patients with preexisting autoimmune disorders are often excluded from clinical trials, although subsequent studies have shown that many of these patients have acceptable ICI tolerance. The safety and efficacy of ICIs among patients with preexisting neurologic autoimmune disorders (NAIDs) is not well characterized. Objective: To evaluate the safety and clinical outcomes associated with ICI therapy among patients with NAIDs. Design, setting, and participants: This multicenter retrospective cohort study included patients with cancer who were treated with ICIs between October 2013 and [...]
Nivolumab plus relatlimab in advanced melanoma: RELATIVITY-047 4-year update.
Abstract Background: In phase 2/3 randomized RELATIVITY-047, nivolumab plus relatlimab demonstrated a statistically significant improvement in progression-free survival (PFS), a clinically meaningful but not statistically significant improvement in overall survival (OS), and a numerically higher objective response rate (ORR) versus nivolumab alone in patients with previously untreated advanced melanoma. Methods: Descriptive 4-year updated analyses in patients treated with nivolumab 480 mg plus relatlimab 160 mg fixed-dose combination versus nivolumab 480 mg intravenously every 4 weeks are presented. Primary endpoint was PFS by blinded independent central review (BICR). Other endpoints included melanoma-specific survival (MSS). Results: At 45.3 months' minimum follow-up, nivolumab plus relatlimab [...]
Combination of encorafenib and binimetinib followed by ipilimumab and nivolumab versus ipilimumab and nivolumab in patients with advanced melanoma with BRAFV600E or BRAFV600K mutations (EBIN): an international, open-label, randomised, controlled, phase 2 study.
Abstract Background: Current first-line treatment for patients with metastatic melanoma with BRAFV600E or BRAFV600K mutations includes immunotherapy with immune checkpoint inhibitors and targeted therapy; however, the optimal sequencing of these treatments is unclear. We aimed to investigate the use of a targeted-therapy induction regimen before treatment with immune checkpoint inhibitors. Methods: This open-label, randomised, controlled, phase 2 trial (EBIN) was conducted at 37 centres in eight European countries. Eligible patients were 18 years or older and had previously untreated, unresectable, stage III or IV melanoma with BRAFV600E or BRAFV600K mutations and an Eastern Cooperative Oncology Group performance status of 0 or 1. Patients were randomly [...]
Surgical considerations for tumour-infiltrating lymphocyte therapy in melanoma: results from a randomized phase III trial.
Abstract Background: The aim of this study was to describe the impact of surgical resections on tumour-infiltrating lymphocyte (TIL) therapy, based on results from a randomized phase III trial comparing TIL therapy with standard ipilimumab in patients with metastatic melanoma (NCT02278887). Methods: Surgical details of all operations performed in the trial were collected. Location, total number, and size of resected metastases were assessed in relation to successful TIL investigational medicinal product (IMP) manufacture and response to TIL therapy. Results: A total of 93 operations were needed to treat 80 patients with TIL therapy. Surgical complications were detected in 17% of operations. These [...]
Diagnostic Potential of 68Ga-NeoB PET/CT with Estrogen Receptor- and Progesterone Receptor-Positive Breast Cancer Undergoing Staging or Restaging for Metastatic Disease.
Abstract Background: 18F-FDG PET/CT has low sensitivity for estrogen receptor and progesterone receptor (ER/PR)-positive breast cancer. By contrast, gastrin-releasing peptide receptor is overexpressed in ER/PR-positive breast cancer. This study assessed the diagnostic potential of 68Ga-NeoB PET/CT in staging or restaging metastatic ER/PR-positive and human epidermal growth factor receptor 2 (HER2)-negative breast cancer. Methods: Patients with ER/PR-positive and HER2-negative breast cancer with clinical suspicion for metastatic disease undergoing staging or restaging were prospectively enrolled. All patients underwent 68Ga-NeoB PET/CT, in addition to standard 18F-FDG PET/CT. ER/PR-positive and HER2-negative status was confirmed in prior biopsy samples (primary or metastatic). Conventional imaging (18F-FDG PET/CT, bone scan, and [...]
ASO Visual Abstract: Cartilage Resection in the Surgical Management of Ear Melanoma.
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Do BRAF-targeted therapies have a role in the era of immunotherapy?
Abstract Over half of cutaneous melanomas have BRAF mutations, with this mutation being more prevalent in younger patients who often present with more aggressive disease. BRAF-targeted therapy and checkpoint inhibitor immunotherapy have led to marked improvements in outcomes for patients with BRAF-mutant melanoma. Despite these advances, novel combinatorial strategies are vital given that more than half of advanced melanoma patients will still die due to melanoma. Translational evidence has suggested potential immunostimulatory effects of BRAF-targeted therapies, yet their combination with immunotherapy has shown limited clinical success. The pathways that lead to acquired resistance to targeted therapy, which may confer [...]
Reflectance confocal microscopy terminology for nonmelanocytic skin lesions: A Delphi consensus of experts.
Abstract Background: There is lack of uniformity in reflectance confocal microscopy (RCM) terminology. Objective: To establish expert consensus on a standardized set of RCM terms that describe non-melanocytic lesions (NMLs). Methods: We invited RCM experts to participate in a Delphi-consensus study. Fifty-nine RCM descriptors were extracted from a previous systematic review on RCM terminology for describing NML. Of these, 35 items were presented as 4 groups of synonymous terms and 24 items as single, nonsynonymous terms. For the first round, an agreement threshold was set at >70%. Participants could also propose new terms. Terms with ≤70% agreement and newly proposed terms were [...]