title: Long term survival with cytotoxic T lymphocyte-associated antigen 4 blockade using tremelimumab.
abstract: OBJECTIVE
  One of the hallmarks of cancer immunotherapy is the long duration of responses, evident with cytokines like interleukin-2 or a variety of cancer vaccines. However, there is limited information available on very long term outcomes of patients treated with anti-cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) antibodies. Tremelimumab is an anti-CTLA-4 antibody of immunoglobulin G2 (IgG2) isotype initially tested in patients with advanced melanoma over 12 years ago.
  
  
  METHODS
  We reviewed the outcomes of patients with advanced melanoma enrolled in four phase 1 and 2 tremelimumab trials at two sites to determine response rates and long-term survival.
  
  
  RESULTS
  A total of 143 patients were enrolled at two institutions from 2002 to 2008. Tremelimumab administration varied between a single dose of 0.01 mg/kg and 15 mg/kg every 3 months. Median overall survival was 13 months (95% confidence interval (CI), 10-16.6), ranging from less than a month to 12+ years. An objective response rate of 15.6% was observed, with median duration of response of 6.5 years, range of 3-136+ months. The Kaplan-Meier estimated 5 year survival rate was 20% (95% CI, 13-26%), with 10 and 12.5 year survival rates of 16% (95% CI, 9-23%).
  
  
  CONCLUSIONS
  CTLA-4 blockade with tremelimumab can lead to very long duration of objective anti-tumour responses beyond 12 years.
authors.affiliation: Department of Medical Oncology, City of Hope National Medical Center, Duarte, CA, USA.
authors.forename: Zeynep
authors.initials: Z
authors.lastname: Eroglu
authors.affiliation: Department of Melanoma Medical Oncology, The University of Texas-MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Dae Won
authors.initials: DW
authors.lastname: Kim
authors.affiliation: Department of Medicine Statistics Core, University of California Los Angeles, Los Angeles, CA, USA.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Wang
authors.affiliation: St. Luke's Medical Center Cancer Center, Houston, TX, USA.
authors.forename: Luis H
authors.initials: LH
authors.lastname: Camacho
authors.affiliation: Department of Medicine, Division of Hematology/Oncology, Jonsson Comprehensive Cancer Center at UCLA, Los Angeles, CA, USA.
authors.forename: Bartosz
authors.initials: B
authors.lastname: Chmielowski
authors.affiliation: Department of Medicine, Division of Hematology/Oncology, Jonsson Comprehensive Cancer Center at UCLA, Los Angeles, CA, USA.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Seja
authors.affiliation: Department of Medicine, Division of Hematology/Oncology, Jonsson Comprehensive Cancer Center at UCLA, Los Angeles, CA, USA.
authors.forename: Arturo
authors.initials: A
authors.lastname: Villanueva
authors.affiliation: Department of Radiology, University of California Los Angeles, Los Angeles, CA, USA.
authors.forename: Kathleen
authors.initials: K
authors.lastname: Ruchalski
authors.affiliation: Department of Medicine, Division of Hematology/Oncology, Jonsson Comprehensive Cancer Center at UCLA, Los Angeles, CA, USA.
authors.forename: John A
authors.initials: JA
authors.lastname: Glaspy
authors.affiliation: Department of Melanoma Medical Oncology, The University of Texas-MD Anderson Cancer Center, Houston, TX, USA; California Pacific Medical Center, San Francisco, CA, USA.
authors.forename: Kevin B
authors.initials: KB
authors.lastname: Kim
authors.affiliation: Department of Melanoma Medical Oncology, The University of Texas-MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Wen-Jen
authors.initials: WJ
authors.lastname: Hwu
authors.affiliation: Department of Medicine, Division of Hematology/Oncology, Jonsson Comprehensive Cancer Center at UCLA, Los Angeles, CA, USA. Electronic address: aribas@mednet.ucla.edu.
authors.forename: Antoni
authors.initials: A
authors.lastname: Ribas
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000276:immunology / Q000627:therapeutic use; D060908:CTLA-4 Antigen / Q000037:antagonists & inhibitors* / Q000276:immunology; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D053208:Kaplan-Meier Estimate; D008297:Male; D008545:Melanoma / Q000276:immunology / Q000401:mortality / Q000628:therapy*; D008875:Middle Aged; D017063:Outcome Assessment, Health Care / Q000379:methods / Q000706:statistics & numerical data; D012074:Remission Induction; D012189:Retrospective Studies; D015996:Survival Rate; D017741:Survivors / Q000706:statistics & numerical data; D013997:Time Factors; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D060908:CTLA-4 Antigen; C520704:tremelimumab
keywords: Anti-CTLA-4 therapy; Immunotherapy; Melanoma; Tremelimumab