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
Citations
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Breathing new life into immunotherapy: review of melanoma, lung and kidney cancer
TL;DR: In addition to being part of the current treatment armamentarium for metastatic melanoma, immune checkpoint blockade is currently undergoing phase III testing in several cancer types.
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Classification of current anticancer immunotherapies
Lorenzo Galluzzi,Erika Vacchelli,José Manuel Bravo-San Pedro,Aitziber Buqué,Laura Senovilla,Elisa E. Baracco,Norma Bloy,Francesca Castoldi,Jean Pierre Abastado,Patrizia Agostinis,Ron N. Apte,Fernando Aranda,Maha Ayyoub,Philipp Beckhove,Jean-Yves Blay,Laura Bracci,Anne Caignard,Chiara Castelli,Federica Cavallo,Estaban Celis,Vincenzo Cerundolo,Aled Clayton,Mario P. Colombo,Lisa M. Coussens,Madhav V. Dhodapkar,Alexander M.M. Eggermont,Douglas T. Fearon,Wolf H. Fridman,Jitka Fucikova,Dmitry I. Gabrilovich,Jérôme Galon,Abhishek D. Garg,François Ghiringhelli,François Ghiringhelli,Giuseppe Giaccone,Giuseppe Giaccone,Eli Gilboa,Sacha Gnjatic,Axel Hoos,Anne Hosmalin,Anne Hosmalin,Anne Hosmalin,Dirk Jäger,Pawel Kalinski,Klas Kärre,Oliver Kepp,Rolf Kiessling,John M. Kirkwood,Eva Klein,Alexander Knuth,Claire E. Lewis,Roland S. Liblau,Roland S. Liblau,Roland S. Liblau,Michael T. Lotze,Enrico Lugli,Jean-Pierre Mach,Fabrizio Mattei,Domenico Mavilio,Ignacio Melero,Cornelis J. M. Melief,E. A. Mittendorf,Lorenzo Moretta,Adekunke Odunsi,Hideho Okada,Anna Karolina Palucka,Marcus E. Peter,Kenneth J. Pienta,Angel Porgador,George C. Prendergast,George C. Prendergast,Gabriel A. Rabinovich,Nicholas P. Restifo,Naiyer A. Rizvi,Catherine Sautès-Fridman,Hans Schreiber,Barbara Seliger,Hiroshi Shiku,Bruno Silva-Santos,Mark J. Smyth,Mark J. Smyth,Daniel E. Speiser,Daniel E. Speiser,Radek Spisek,Pramod K. Srivastava,James E. Talmadge,Eric Tartour,Sjoerd H. van der Burg,Benoît Van den Eynde,Benoît Van den Eynde,Richard G. Vile,Hermann Wagner,Jeffrey S. Weber,Theresa L. Whiteside,Jedd D. Wolchok,Jedd D. Wolchok,Laurence Zitvogel,Weiping Zou,Guido Kroemer +98 more
TL;DR: A critical, integrated classification of anticancer immunotherapies is proposed and the clinical relevance of these approaches is discussed.
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MHC proteins confer differential sensitivity to CTLA-4 and PD-1 blockade in untreated metastatic melanoma
Scott J. Rodig,Scott J. Rodig,Daniel Gusenleitner,Donald G. Jackson,Evisa Gjini,Anita Giobbie-Hurder,Chelsea Jin,Han Chang,Scott B. Lovitch,Christine Horak,Jeffrey S. Weber,Jason L. Weirather,Jedd D. Wolchok,Michael A. Postow,Michael A. Postow,Anna C. Pavlick,Jason Chesney,F. Stephen Hodi +17 more
TL;DR: It is shown that MHC class I expression in advanced melanoma predicted resistance to anti–CTLA-4, but not anti-PD-1, treatment, which may need MHCclass II to be effective, which explains why patients on combined therapy do better on average, with one drug overcoming the limitations of the other.
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Nanoparticle-Based Immunotherapy for Cancer
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Immune evasion mediated by PD-L1 on glioblastoma-derived extracellular vesicles
Franz Ricklefs,Franz Ricklefs,Quazim A. Alayo,Harald Krenzlin,Ahmad Bakur Mahmoud,Ahmad Bakur Mahmoud,Maria C. Speranza,Maria C. Speranza,Hiroshi Nakashima,Josie Hayes,Kyungheon Lee,Leonora Balaj,Carmela Passaro,Arun K. Rooj,Susanne Krasemann,Bob S. Carter,Clark C. Chen,Tyler Steed,Jeffrey M. Treiber,Scott J. Rodig,Katherine Yang,Ichiro Nakano,Hakho Lee,Ralph Weissleder,Xandra O. Breakefield,Jakub Godlewski,Manfred Westphal,Katrin Lamszus,Gordon J. Freeman,Agnieszka Bronisz,Sean E. Lawler,E. Antonio Chiocca +31 more
TL;DR: Results suggest that PD-L1 on EVs may be another mechanism for glioblastoma to suppress antitumor immunity and support the potential of EVs as biomarkers in tumor patients.
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