title: Ipilimumab experience in heavily pretreated patients with melanoma in an expanded access program at the University Hospital of Siena (Italy).
abstract: OBJECTIVE
  To evaluate the feasibility of ipilimumab treatment for metastatic melanoma outside the boundaries of clinical trials, in a setting similar to that of daily practice.
  
  
  METHODS
  Ipilimumab was available upon physician request in the Expanded Access Programme for patients with life-threatening, unresectable stage III/IV melanoma who failed or did not tolerate previous treatments and for whom no therapeutic option was available. Induction treatment with ipilimumab 10 mg/kg was administered intravenously every 3 weeks, for a total of 4 doses, with maintenance doses every 12 weeks based on physicians' discretion and clinical judgment. Tumors were assessed at baseline, Week 12, and every 12 weeks thereafter per mWHO response criteria, and clinical response was scored as complete response (CR), partial response (PR), stable disease (SD), or progressive disease. Durable disease control (DC) was defined as SD at least 24 weeks from the first dose, CR, or PR.
  
  
  RESULTS
  Disease control rate at 24 and 60 weeks was 29.6% and 15%, respectively. Median overall survival at a median follow-up of 8.5 months was 9 months. The 1- and 2-year survival rates were 34.8% and 23.5%, respectively. Changes in lymphocyte count slope and absolute number during ipilimumab treatment appear to correlate with clinical response and survival, respectively. Adverse events were predominantly immune related, manageable, and generally reversible. One patient died from pancytopenia, considered possibly treatment related.
  
  
  CONCLUSIONS
  Ipilimumab was a feasible treatment for malignant melanoma in heavily pretreated, progressing patients. A sizeable proportion of patients experienced durable DC, including benefits to long-term survival.
authors.affiliation: Medical Oncology and Immunotherapy, University Hospital of Siena, Istituto Toscano Tumori, Strada delle Scotte, 53100, Siena, Italy.
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Di Giacomo
authors.forename: Riccardo
authors.initials: R
authors.lastname: Danielli
authors.forename: Luana
authors.initials: L
authors.lastname: Calabrò
authors.forename: Erica
authors.initials: E
authors.lastname: Bertocci
authors.forename: Chiara
authors.initials: C
authors.lastname: Nannicini
authors.forename: Diana
authors.initials: D
authors.lastname: Giannarelli
authors.forename: Angelo
authors.initials: A
authors.lastname: Balestrazzi
authors.forename: Francesco
authors.initials: F
authors.lastname: Vigni
authors.forename: Valentina
authors.initials: V
authors.lastname: Riversi
authors.forename: Clelia
authors.initials: C
authors.lastname: Miracco
authors.forename: Maurizio
authors.initials: M
authors.lastname: Biagioli
authors.forename: Maresa
authors.initials: M
authors.lastname: Altomonte
authors.forename: Michele
authors.initials: M
authors.lastname: Maio
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D000074324:Ipilimumab; D007558:Italy; D053208:Kaplan-Meier Estimate; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008875:Middle Aged; D009367:Neoplasm Staging; D016016:Proportional Hazards Models; D016879:Salvage Therapy / Q000379:methods; D012878:Skin Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000473:pathology; D016896:Treatment Outcome; D014604:Uveal Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000473:pathology; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D000074324:Ipilimumab