title: CTLA-4 blockade with ipilimumab: long-term follow-up of 177 patients with metastatic melanoma.
abstract: OBJECTIVE
  Treatment with ipilimumab can cause objective tumor responses in patients with metastatic melanoma. We have treated 177 evaluable patients in three clinical trials and have long-term follow-up to evaluate the durability of responses.
  
  
  METHODS
  Patients with metastatic melanoma were treated in three trials from 2002 to 2005. In protocol 1, 56 patients received ipilimumab with gp100 peptides. In protocol 2, 36 patients received ipilimumab with interleukin-2. In protocol 3, 85 patients received ipilimumab with intrapatient dose-escalation and were randomized to receive gp100 peptides. We have analyzed their long-term follow-up and survival data.
  
  
  RESULTS
  With median follow-up for protocols 1, 2, and 3 being 92, 84, and 71 months, median survival was 14, 16, and 13 months with 5-year survival rates being 13%, 25%, and 23%, respectively. Patients in protocol 2 had a 17% complete response (CR) rate, compared with 7% in protocol 1 and 6% in protocol 3. These CR rates are higher than previously reported for the same trials because some patients who eventually became complete responders had continual tumor regression months to years after therapy. All but one of the 15 complete responders are ongoing at 54+ to 99+ months.
  
  
  CONCLUSIONS
  This report provides the longest follow-up of patients with melanoma treated with ipilimumab and shows that ipilimumab can induce durable, potentially curative tumor regression in a small percentage of patients with metastatic melanoma. The combination of ipilimumab and interleukin-2 seems to have an increased CR rate, but this needs to be tested in a randomized trial.
authors.affiliation: Surgery Branch, National Cancer Institute, NIH, Bldg 10-CRC, Room 3-5760, 10 Center Drive, Bethesda, MD 20892, USA.
authors.forename: Peter A
authors.initials: PA
authors.lastname: Prieto
authors.forename: James C
authors.initials: JC
authors.lastname: Yang
authors.forename: Richard M
authors.initials: RM
authors.lastname: Sherry
authors.forename: Marybeth S
authors.initials: MS
authors.lastname: Hughes
authors.forename: Udai S
authors.initials: US
authors.lastname: Kammula
authors.forename: Donald E
authors.initials: DE
authors.lastname: White
authors.forename: Catherine L
authors.initials: CL
authors.lastname: Levy
authors.forename: Steven A
authors.initials: SA
authors.lastname: Rosenberg
authors.forename: Giao Q
authors.initials: GQ
authors.lastname: Phan
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D060908:CTLA-4 Antigen / Q000037:antagonists & inhibitors* / Q000276:immunology; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000009:adverse effects; D002986:Clinical Trials as Topic; D003872:Dermatitis / Q000209:etiology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007376:Interleukin-2 / Q000008:administration & dosage / Q000009:adverse effects; D000074324:Ipilimumab; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D008875:Middle Aged; D009362:Neoplasm Metastasis; D010900:Pituitary Diseases / Q000139:chemically induced; D016019:Survival Analysis; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D060908:CTLA-4 Antigen; D019496:Cancer Vaccines; D007376:Interleukin-2; D000074324:Ipilimumab; C544395:gp100(209-2M) vaccine