title: A Pilot Study of Anti-CTLA4 Antibody Ipilimumab in Patients with Synovial Sarcoma.
abstract: Background. Patients with recurrent synovial sarcomas have few options for systemic therapy. Since they express large amounts of endogenous CT (cancer testis) antigens such as NY-ESO-1, we investigated the clinical activity of single agent anti-CTLA4 antibody ipilimumab in patients with advanced or metastatic synovial sarcoma. Methods. A Simon two-stage phase II design was used to determine if there was sufficient activity to pursue further. The primary endpoint was tumor response rate by RECIST 1.0. Patients were treated with ipilimumab 3 mg/kg intravenously every 3 weeks for three cycles and then restaged. Retreatment was possible for patients receiving an extra three-week break from therapy. Sera and peripheral blood mononuclear cells were collected before and during therapy to assess NY-ESO-1-specific immunity. Results. Six patients were enrolled and received 1-3 cycles of ipilimumab. All patients showed clinical or radiological evidence of disease progression after no more than three cycles of therapy, for a RECIST response rate of 0%. The study was stopped for slow accrual, lack of activity, and lack of immune response. There was no evidence of clinically significant either serologic or delayed type hypersensitivity responses to NY-ESO-1 before or after therapy. Conclusion. Despite high expression of CT antigens by synovial sarcomas of patients treated in this study, there was neither clinical benefit nor evidence of anti-CT antigen serological responses. Assessment of the ability of synovial sarcoma cell lines to present cancer-germ cell antigens may be useful in determining the reason for the observed lack of immunological or clinical activity.
authors.affiliation: Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA ; Departments of Medicine, Pediatrics, and Orthopaedics, Mount Sinai School of Medicine, 1 Gustave L. Levy Place, P.O. Box 1208, New York, NY 10029-6574, USA.
authors.forename: Robert G
authors.initials: RG
authors.lastname: Maki
authors.forename: Achim A
authors.initials: AA
authors.lastname: Jungbluth
authors.forename: Sacha
authors.initials: S
authors.lastname: Gnjatic
authors.forename: Gary K
authors.initials: GK
authors.lastname: Schwartz
authors.forename: David R
authors.initials: DR
authors.lastname: D'Adamo
authors.forename: Mary Louise
authors.initials: ML
authors.lastname: Keohan
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Wagner
authors.forename: Kelly
authors.initials: K
authors.lastname: Scheu
authors.forename: Rita
authors.initials: R
authors.lastname: Chiu
authors.forename: Erika
authors.initials: E
authors.lastname: Ritter
authors.forename: Jennifer
authors.initials: J
authors.lastname: Kachel
authors.forename: Israel
authors.initials: I
authors.lastname: Lowy
authors.forename: Lloyd J
authors.initials: LJ
authors.lastname: Old
authors.forename: Gerd
authors.initials: G
authors.lastname: Ritter
references.citation: Proc Natl Acad Sci U S A. 2000 Apr 25;97(9):4760-5
references.pmid: 10781081
references.citation: Ann Surg. 2007 Jul;246(1):105-13
references.pmid: 17592298
references.citation: Hum Mol Genet. 1994 May;3(5):745-9
references.pmid: 8081361
references.citation: J Immunol. 2002 Aug 1;169(3):1611-8
references.pmid: 12133991
references.citation: J Transl Med. 2009 Jun 12;7:44
references.pmid: 19523231
references.citation: Cancer Genet Cytogenet. 2009 Nov;195(1):54-8
references.pmid: 19837269
references.citation: J Immunother. 2012 Jan;35(1):89-97
references.pmid: 22130166
references.citation: Hum Pathol. 2002 Feb;33(2):225-9
references.pmid: 11957149
references.citation: N Engl J Med. 2011 Jun 30;364(26):2517-26
references.pmid: 21639810
references.citation: J Clin Oncol. 2005 Jan 20;23(3):576-84
references.pmid: 15659504
references.citation: Nat Genet. 1994 Aug;7(4):502-8
references.pmid: 7951320
references.citation: Nat Rev Clin Oncol. 2011 Aug 02;8(10):577-85
references.pmid: 21808266
references.citation: Proc Natl Acad Sci U S A. 2003 Mar 4;100(5):2651-6
references.pmid: 12601173
references.citation: J Clin Oncol. 1993 Jul;11(7):1269-75
references.pmid: 8315424
references.citation: Proc Natl Acad Sci U S A. 2003 Jul 22;100(15):8862-7
references.pmid: 12853579
references.citation: Sarcoma. 2011;2011:231789
references.pmid: 21559258
references.citation: J Transl Med. 2005 Jan 12;3(1):1
references.pmid: 15647119
references.citation: Oncogene. 2001 Sep 10;20(40):5755-62
references.pmid: 11607825
references.citation: J Clin Oncol. 2011 Mar 1;29(7):917-24
references.pmid: 21282551
references.citation: N Engl J Med. 2010 Aug 19;363(8):711-23
references.pmid: 20525992
references.citation: Control Clin Trials. 1989 Mar;10(1):1-10
references.pmid: 2702835
references.citation: N Engl J Med. 2012 Jun 28;366(26):2443-54
references.pmid: 22658127
references.citation: Int J Cancer. 2001 Oct 15;94(2):252-6
references.pmid: 11668506
references.citation: Sarcoma. 2012;2012:249219
references.pmid: 22550415
references.citation: Core Evid. 2010 Jun 15;4:191-8
references.pmid: 20694075
references.citation: J Exp Med. 1998 Apr 20;187(8):1349-54
references.pmid: 9547346
references.citation: Cancer Immun. 2005 Feb 01;5:2
references.pmid: 15683221
references.citation: Lancet. 2012 May 19;379(9829):1879-86
references.pmid: 22595799
references.citation: Cancer Sci. 2008 Feb;99(2):368-75
references.pmid: 18271936
references.citation: Clin Cancer Res. 2009 Dec 1;15(23):7412-20
references.pmid: 19934295
references.citation: Cancer Immun. 2004 Aug 09;4:7
references.pmid: 15298487
references.citation: Genes Chromosomes Cancer. 2001 Jan;30(1):1-14
references.pmid: 11107170
references.citation: Proc Natl Acad Sci U S A. 2011 Oct 4;108(40):16723-8
references.pmid: 21933959
references.citation: Cancer Immun. 2004 Jan 23;4:1
references.pmid: 14738373
references.citation: J Clin Oncol. 2000 Nov 15;18(22):3794-803
references.pmid: 11078492
references.citation: Mod Pathol. 2012 Jun;25(6):854-8
references.pmid: 22388761
references.citation: J Clin Oncol. 2000 May;18(10):2087-94
references.pmid: 10811674