Immune checkpoint blockade (ICB) agents are prominent immunotherapies for the treatment of advanced melanoma. However, they fail to promote any durable clinical benefit in a large cohort of patients. This study assessed clinical and molecular predictors of ICB response and survival in advanced melanoma. A retrospective analysis was performed on 210 patients treated with PD-1 or CTLA-4 inhibitors at Barretos Cancer Hospital, Brazil. PD-L1 expression was assessed by immunohistochemistry using formalin-fixed paraffin-embedded tumor tissues collected prior to ICB therapy. Patients were divided into responders (complete and partial response and stable disease for more than 6 months) and non-responders (stable disease for less than 6 months and progressive disease). Among them, about 82% underwent anti-PD-1 immunotherapy, and 60.5% progressed after the ICB treatment. Patients that received ICB as first-line therapy showed higher response rates than previously treated patients. Higher response rates were further associated with superficial spreading melanomas and positive PD-L1 expression (>1%). Likewise, PD-L1 positive expression and V600 mutations were associated with a higher overall survival after ICB therapy. Since ICBs are expensive therapies, evaluation of PD-L1 tumor expression in melanoma patients should be routinely assessed to select patients that are most likely to respond.
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http://dx.doi.org/10.3390/diagnostics13061041 | DOI Listing |
BMJ Case Rep
January 2025
Hematology/Oncology, Walter Reed National Military Medical Center, Bethesda, Maryland, USA.
Carcinoma of unknown primary (CUP) comprises 2-5% of cancer diagnoses worldwide, with a prevalence that has modestly declined with increased availability of advanced diagnostic tools such as next-generation sequencing (NGS). This case presentation illustrates the possibilities and gaps that remain with improving diagnostic capabilities in identifying and effectively treating CUP. This is the case of a rapidly enlarging right axillary mass without a primary tumour site and histological evaluation demonstrating a poorly differentiated neoplasm.
View Article and Find Full Text PDFNat Med
January 2025
BioNTech US, Cambridge, MA, USA.
New treatment approaches are warranted for patients with advanced melanoma refractory to immune checkpoint blockade (ICB) or BRAF-targeted therapy. We designed BNT221, a personalized, neoantigen-specific autologous T cell product derived from peripheral blood, and tested this in a 3 + 3 dose-finding study with two dose levels (DLs) in patients with locally advanced or metastatic melanoma, disease progression after ICB, measurable disease (Response Evaluation Criteria in Solid Tumors version 1.1) and, where appropriate, BRAF-targeted therapy.
View Article and Find Full Text PDFCancer Immunol Immunother
January 2025
Department of Dermatology and National Center for Tumor Diseases (NCT), Medical Faculty Heidelberg, NCT Heidelberg, a partnership between DKFZ and University Hospital Heidelberg, Heidelberg University, Heidelberg, Germany.
Cytomegalovirus (CMV) infection or reactivation in immune-compromised individuals can lead to a wide range of severe complications including hepatitis. However, its relation with immune checkpoint inhibitors (ICIs) induced hepatitis (ICI-hepatitis) and tumor responses in advanced melanoma patients remains unclear. Hundred and ninety metastatic cutaneous melanoma patients (mCM) who received ICI treatment, with CMV IgG or IgM information available at baseline, were included in the study (Cohort 1).
View Article and Find Full Text PDFMol Pharm
January 2025
NHC Key Laboratory of Nuclear Medicine, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi 214063, China.
Melanoma, with its steadily rising global incidence, is characterized by high invasiveness, leading to poor prognosis in advanced stages. There remains an unmet clinical need for the development of radiolabeled PET imaging probes for the early diagnosis of melanoma. Integrin VLA-4, a key factor in melanoma metastasis, presents a promising protein target to address the specificity shortcomings of existing probes in melanoma imaging.
View Article and Find Full Text PDFJ Dtsch Dermatol Ges
January 2025
Department of Dermatology, University Hospital Tuebingen, Tuebingen, Germany.
Background: Up to now, the optimal duration of immune checkpoint inhibitors (ICI) has not been evaluated in prospective studies. However, current clinical practice requires decisions to be made regarding the duration of ICI in complete responders.
Material And Methods: A survey was sent to 80 DeCOG skin cancer centers to assess how decisions are made on treatment duration of ICI in melanoma after having reached complete response, and staging intervals after ICI discontinuation.
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