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High peripheral T cell diversity is associated with lower risk of toxicity and superior response to dual immune checkpoint inhibitor therapy in patients with metastatic NSCLC.
J Immunother Cancer
December 2024
Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Introduction: Despite significant successes, immune checkpoint blockade fails to achieve clinical responses in a significant proportion of patients, predictive markers for responses are imperfect and immune-related adverse events (irAEs) are unpredictable. We used T-cell receptor (TCR) sequencing to systematically analyze prospectively collected patient blood samples from a randomized clinical trial of dual immune checkpoint inhibitor therapy to evaluate changes in the T-cell repertoire and their association with response and irAEs.
Methods: Patients with immunotherapy-naïve metastatic non-small cell lung cancer (NSCLC) were treated with ipilimumab and nivolumab according to trial protocol (LONESTAR, NCT03391869).
Advances in cancer treatments have significantly improved their effectiveness, yet access to first-line therapies remains limited. A 2017 survey revealed that over 25 % of metastatic melanoma patients in Europe lacked access to recommended therapies. To address this, the European Association of Dermato-Oncology and the European Melanoma Registry conducted a follow-up study on the registration and reimbursement of first-line treatments.
View Article and Find Full Text PDFGaps in the management of adrenal insufficiency in melanoma survivors: a retrospective cohort study.
EClinicalMedicine
January 2025
Division of Endocrinology, Diabetes and Hypertension, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Background: Due to limited data on managing immunotherapy-induced secondary adrenal insufficiency (SAI) in melanoma survivors, this study investigated its management strategies and outcomes.
Methods: This retrospective cohort study analyzed melanoma patients treated with immune checkpoint inhibitors (ICIs) with SAI (Mel_SAI, n = 161), without SAI (Mel_CON, n = 168), and patients with pituitary adenoma-related SAI (Pit_SAI, n = 106) at our institution from January 2013 to November 2023. We compared glucocorticoid management patterns, quality of life using distress scores, and the impact of different glucocorticoid types on survival outcomes using Kaplan-Meier analysis.
vCPP2319 interacts with metastatic breast cancer extracellular vesicles (EVs) and transposes a human blood-brain barrier model.
Heliyon
December 2024
Gulbenkian Institute for Molecular Medicine, Faculdade de Medicina da Universidade de Lisboa, Av. Prof. Egas Moniz, Lisbon, 1649-028, Portugal.
Brain metastases (BM) are frequently found in cancer patients and, though their precise incidence is difficult to estimate, there is evidence for a correlation between BM and specific primary cancers, such as lung, breast, and skin (melanoma). Among all these, breast cancer is the most frequently diagnosed among women and, in this case, BM cause a critical reduction of the overall survival (OS), especially in triple negative breast cancer (TNBC) patients. The main challenge of BM treatment is the impermeable nature of the blood-brain barrier (BBB), which shields the central nervous systems (CNS) from chemotherapeutic drugs.
View Article and Find Full Text PDFWhen to stop immunotherapy for advanced melanoma: the emulated target trials.
EClinicalMedicine
December 2024
AP-HP Hotel-Dieu Hospital, Centre de Recherche épidémiologie et Statistiques (CRESS-UMR1153), Centre d'épidémiologie Clinique, Inserm / Université Paris Cité / AP-HP, Centre Virchow-Villermé, Centre Equator France, Paris, France.
Background: Immune checkpoint inhibitors (ICIs) have demonstrated their efficacy with a 7.5-year overall survival (OS) close to 50% for advanced stages. The design of clinical trials provides for treatment until progression or toxicity, or for a maximum duration of two years.
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