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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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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Long-term follow-up of ipilimumab-induced hypophysitis, a common adverse event of the anti-CTLA-4 antibody in melanoma
Frédérique Albarel,C. Gaudy,Frederic Castinetti,Tiphaine Carré,Isabelle Morange,Bernard Conte-Devolx,Jean-Jacques Grob,Thierry Brue +7 more
TL;DR: Ipilimumab-induced hypophysitis is a common side-effect with frequent hormonal deficiencies at diagnosis and patients receiving these immunomodulatory therapies should be closely monitored especially by systematic baseline hormone measurements after the third infusion and remain at a risk of adrenal insufficiency in the long-term.
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Myeloid-Derived Suppressor Cells Predict Survival of Patients with Advanced Melanoma: Comparison with Regulatory T Cells and NY-ESO-1- or Melan-A–Specific T Cells
Benjamin Weide,Alexander Martens,Henning Zelba,Christina Stutz,Evelyna Derhovanessian,Anna Maria Di Giacomo,Michele Maio,Antje Sucker,Bastian Schilling,Dirk Schadendorf,Petra Buttner,Claus Garbe,Graham Pawelec +12 more
TL;DR: Circulating MDSC-depleting strategies in the therapeutic setting especially in combination with vaccination or T-cell transfer approaches have a negative impact on survival and inversely correlate with the presence of functional antigen–specific T cells in patients with advanced melanoma.
Journal ArticleDOI
Baseline Tumor Size Is an Independent Prognostic Factor for Overall Survival in Patients with Melanoma Treated with Pembrolizumab.
Richard W. Joseph,Jeroen Elassaiss-Schaap,Richard F. Kefford,Richard F. Kefford,Wen-Jen Hwu,Jedd D. Wolchok,Anthony M. Joshua,Antoni Ribas,F. Stephen Hodi,Omid Hamid,Caroline Robert,Adil Daud,Roxana S. Dronca,Peter Hersey,Jeffrey S. Weber,Amita Patnaik,Dinesh P. de Alwis,Andrea Marie Perrone,Jin Zhang,S. Peter Kang,Scot Ebbinghaus,Keaven M. Anderson,Tara C. Gangadhar +22 more
TL;DR: In this paper, the authors assess the association of baseline tumor size with other baseline clinical factors and outcomes in pembrolizumab-treated patients with advanced melanoma in KEYNOTE-001 (NCT01295827).
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Prognostic implications of immunosuppressive protein expression in tumors as well as immune cell infiltration within the tumor microenvironment in gastric cancer
Jin Won Kim,Kyung Han Nam,Sang Hoon Ahn,Do Joong Park,Hyung Ho Kim,Se Hyun Kim,Hyun Chang,Jeong Ok Lee,Yu Jung Kim,Hye Seung Lee,Jee Hyun Kim,Soo Mee Bang,Jong Seok Lee,Keun Wook Lee +13 more
TL;DR: GC patients with immunosuppressive protein expression (PD-L1, CTLA-4, or IDO) had distinct clinicopathological characteristics and in multivariate analysis, these two immune markers had a prognostic impact on survival, independent of other clinical variables.
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Blockade of the PD-1/PD-L1 axis augments lysis of AML cells by the CD33/CD3 BiTE antibody construct AMG 330: reversing a T-cell-induced immune escape mechanism.
Christina Krupka,Peter Kufer,Roman Kischel,Gerhard Zugmaier,Felix S. Lichtenegger,Thomas Köhnke,Binje Vick,Irmela Jeremias,Klaus H. Metzeler,Torben Altmann,Stephanie Schneider,Michael Fiegl,Karsten Spiekermann,Karsten Spiekermann,Patrick Bäuerle,Wolfgang Hiddemann,Wolfgang Hiddemann,Gert Riethmüller,Marion Subklewe +18 more
TL;DR: The results support the evaluation of checkpoint molecules in upcoming clinical trials with AMG 330 to enhance BiTE antibody construct-mediated cytotoxicity and characterized a critical resistance mechanism employed by primary AML cells under AMg 330-mediated proinflammatory conditions.
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