title: Effectiveness and tolerability of ipilimumab: experiences from 198 patients included in a named-patient program in various daily-practice settings and multiple institutions.
abstract: BACKGROUND
  Ipilimumab is an approved anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody introducing immune responses in melanoma patients. Treatment experiences from named-patient programs support the evaluation of the efficacy and tolerability of new medicines under usual circumstances of health care practice. Here, the largest ever reported cohort treated with ipilimumab 3 mg/kg alone is described.
  
  
  METHODS
  This report retrospectively analyzes data of 198 patients who were followed up in 15 hospital centers in Germany between April 2010 and March 2013. Patients had received prior therapy for unresectable stage III or IV melanoma before receiving ipilimumab (4 doses of 3 mg/kg every 21 d). Routine staging and tumor response evaluation procedures were applied.
  
  
  RESULTS
  Of the patients, 119 received the planned 4-course therapy schedule; in further 79 patients, the number of doses was reduced mainly because of toxicity or fast progression. In all, 196 patients were eligible for evaluation of the efficacy of ipilimumab under routine care conditions. Median overall survival (OS) was 6.8 months [95% confidence interval, 5.6-10.3] from the start of therapy. OS differed significantly among patients who received 4 doses (n=119) and those receiving <4 doses (n=79) (14.2 vs. 2.0 mo; P<0.0001). The overall response rate (ORR) of 11% was in the same range as reported from previous clinical trials; and stable disease (SD) was observed in 11% resulting in a disease control rate (ORR+SD) of 22%. In 23 of the 79 patients with reduced dosing, dose omission was most probably caused by toxicity, whereas 56 patients had progressive disease before receiving all 4 treatment cycles. Immune-related adverse events (irAE) were reported in 30% of all treated patients, the occurrence of irAE correlated significantly with the probability of response to therapy and prolonged OS.
  
  
  CONCLUSIONS
  In this named-patient program including heavily pretreated patients, the efficacy and tolerability of ipilimumab 3 mg/kg corresponds with findings from the confirmatory clinical trial.
authors: *Department of Dermatology, Center for Dermatooncology, University Medical Center Tübingen, Tübingen †Department of Dermatology and Venerology, Skin Cancer Center and Center for Integrated Oncology, University Hospital of Cologne, CIO Köln Bonn ‡Department of Dermatology, University Hospital Heidelberg, Heidelberg §Department of Dermatology, University Hospital Mainz, Mainz ∥Department of Dermatology, University Essen-Duisburg, Essen ¶Department of Dermatology and Allergy, Hannover Medical School, Hannover #Department of Dermatology, University Hospital Frankfurt am Main, Frankfurt/Main **Department of Dermatology, Elbe Kliniken Buxtehude, Buxtehude ††Medical Department, Technische Universität, München ‡‡Department of Dermatology, Zentralklinikum Augsburg, Augsburg §§Department of Dermatology, Harzklinikum Dorothea Christiane Erxleben, Quedlinburg ∥∥Department of Dermatology, University Hospital Muenster, Münster ¶¶Department of Dermatology, University Hospital Kiel, Kiel ##Department of Dermatology, University Hospital Homburg/Saar, Homburg/Saar ***Department of Dermatology, University Hospital Erlangen, Erlangen, Germany.
authors: Thomas K
authors: TK
authors: Eigentler
authors: Max
authors: M
authors: Schlaak
authors: Jessica C
authors: JC
authors: Hassel
authors: Carmen
authors: C
authors: Loquai
authors: Ingo
authors: I
authors: Stoffels
authors: Ralf
authors: R
authors: Gutzmer
authors: Sylvie
authors: S
authors: Pätzold
authors: Peter
authors: P
authors: Mohr
authors: Ulrich
authors: U
authors: Keller
authors: Hans
authors: H
authors: Starz
authors: Jens
authors: J
authors: Ulrich
authors: Athanasios
authors: A
authors: Tsianakas
authors: Katharina
authors: K
authors: Kähler
authors: Axel
authors: A
authors: Hauschild
authors: Eva
authors: E
authors: Janssen
authors: Beatrice
authors: B
authors: Schuler-Thurner
authors: Benjamin
authors: B
authors: Weide
authors: Claus
authors: C
authors: Garbe
mesh_terms: D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D000074324:Ipilimumab; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D000074324:Ipilimumab