Improved Survival with Ipilimumab in Patients with Metastatic Melanoma.
F. Stephen Hodi,Steven J. O'Day,David F. McDermott,R. W. Weber,Jeffrey A. Sosman,John B. A. G. Haanen,Rene Gonzalez,Caroline Robert,Dirk Schadendorf,Jessica C. Hassel,Wallace Akerley,Alfons J.M. van den Eertwegh,Jose Lutzky,Paul Lorigan,Julia Vaubel,Gerald P. Linette,David W. Hogg,Christian H. Ottensmeier,Céleste Lebbé,Christian Peschel,Ian Quirt,Joseph I. Clark,Jedd D. Wolchok,Jeffrey S. Weber,Jason Tian,Michael Yellin,Geoffrey M. Nichol,Axel Hoos,Walter J. Urba +28 more
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TLDR
Ipilimumab, with or without a gp100 peptide vaccine, as compared with gp100 alone, improved overall survival in patients with previously treated metastatic melanoma.Abstract:
Background An improvement in overall survival among patients with metastatic melanoma has been an elusive goal. In this phase 3 study, ipilimumab — which blocks cytotoxic T-lymphocyte–associated antigen 4 to potentiate an antitumor T-cell response — administered with or without a glycoprotein 100 (gp100) peptide vaccine was compared with gp100 alone in patients with previously treated metastatic melanoma. Methods A total of 676 HLA-A*0201–positive patients with unresectable stage III or IV melanoma, whose disease had progressed while they were receiving therapy for metastatic disease, were randomly assigned, in a 3:1:1 ratio, to receive ipilimumab plus gp100 (403 patients), ipilimumab alone (137), or gp100 alone (136). Ipilimumab, at a dose of 3 mg per kilogram of body weight, was administered with or without gp100 every 3 weeks for up to four treatments (induction). Eligible patients could receive reinduction therapy. The primary end point was overall survival. Results The median overall survival was 10.0 months among patients receiving ipilimumab plus gp100, as compared with 6.4 months among patients receiving gp100 alone (hazard ratio for death, 0.68; P<0.001). The median overall survival with ipilimumab alone was 10.1 months (hazard ratio for death in the comparison with gp100 alone, 0.66; P = 0.003). No difference in overall survival was detected between the ipilimumab groups (hazard ratio with ipilimumab plus gp100, 1.04; P = 0.76). Grade 3 or 4 immune-related adverse events occurred in 10 to 15% of patients treated with ipilimumab and in 3% treated with gp100 alone. There were 14 deaths related to the study drugs (2.1%), and 7 were associated with immune-related adverse events. Conclusions Ipilimumab, with or without a gp100 peptide vaccine, as compared with gp100 alone, improved overall survival in patients with previously treated metastatic melanoma. Adverse events can be severe, long-lasting, or both, but most are reversible with appropriate treatment. (Funded by Medarex and Bristol-Myers Squibb; ClinicalTrials.gov number, NCT00094653.)read more
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Cross-talk between myeloid-derived suppressor cells (MDSC), macrophages, and dendritic cells enhances tumor-induced immune suppression
TL;DR: The cell-cell interactions used by MDSC to inhibit anti-tumor immunity and promote progression are reviewed, and the role of inflammation in promoting cross-talk between M DSC and other cells in the tumor microenvironment is reviewed.
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CTLA-4 Blockade with Ipilimumab: Long-term Follow-up of 177 Patients with Metastatic Melanoma
Peter A. Prieto,James Chih-Hsin Yang,Richard M. Sherry,Michael S. Hughes,Udai S. Kammula,Donald E. White,Catherine Levy,Steven A. Rosenberg,Giao Q. Phan +8 more
TL;DR: This report shows that ipilimumab can induce durable, potentially curative tumor regression in a small percentage of patients with metastatic melanoma and seems to have an increased CR rate, but this needs to be tested in a randomized trial.
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Prognostic Factors for Survival in Melanoma Patients with Brain Metastases
Michael A. Davies,Ping Liu,Susan McIntyre,Kevin B. Kim,Nicholas Papadopoulos,Wen-Jen Hwu,Patrick Hwu,Agop Y. Bedikian +7 more
TL;DR: The outcomes of advanced melanoma patients who developed brain metastases were reviewed to identify significant prognostic factors for overall survival (OS).
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Baseline Peripheral Blood Biomarkers Associated with Clinical Outcome of Advanced Melanoma Patients Treated with Ipilimumab.
Alexander Martens,Kilian Wistuba-Hamprecht,Marnix H Geukes Foppen,Jianda Yuan,Michael A. Postow,Phillip Wong,Emanuela Romano,Amir Khammari,Brigitte Dréno,Mariaelena Capone,Paolo A. Ascierto,Anna Maria Di Giacomo,Michele Maio,Bastian Schilling,Antje Sucker,Dirk Schadendorf,Jessica C. Hassel,Thomas Eigentler,Peter Martus,Jedd D. Wolchok,Christian U. Blank,Graham Pawelec,Claus Garbe,Benjamin Weide +23 more
TL;DR: A baseline signature of low LDH, AMC, and MDSCs as well as high AEC, Tregs, and RLC is associated with favorable outcome following ipilimumab.
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Anti-angiogenesis for cancer revisited: Is there a role for combinations with immunotherapy?
TL;DR: Judicious dosing of anti-angiogenic treatment can transiently normalize the tumor vasculature by decreasing vascular permeability and improving tumor perfusion and blood flow, and synergize with immunotherapy in this time window.
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