title: Clinical and immunohistochemical features associated with a response to bortezomib in patients with multiple myeloma.
abstract: OBJECTIVE
  Multiple myeloma is an incurable disease with heterogeneous clinical behavior. Bortezomib has offered some patients with relapsed and refractory disease an opportunity for prolonged survival. However, there remains a paucity of data in patients treated with bortezomib that accurately delineates and identifies such patients. This information is crucial to guide management.
  
  
  METHODS
  In this study, we aimed to identify the patients most likely to respond to bortezomib salvage therapy. We analyzed the baseline clinical variables and profiled the baseline expression of a broad range of immunohistochemical markers of cell cycle activity, apoptosis, and angiogenesis in a large cohort of multiply relapsed myeloma patients recruited to one of two prospective multicentre trials assessing the efficacy of bortezomib salvage therapy.
  
  
  RESULTS
  Using the European Group for Bone Marrow Transplantation criteria, response (complete or partial) to bortezomib salvage therapy was associated with a previous history of complete response to alternative antimyeloma treatment. Patients who expressed cyclin D1 were more likely to achieve a response. In contrast, patients who expressed p16(INK4A), cytoplasmic p53, and the highest intensity of Bcl-2 staining had a poor response. Patients who achieved a response to bortezomib and those patients who expressed cyclin D1 at baseline showed a significant survival advantage. Patients who expressed FGFR3, a poor prognostic marker, responded equally well and had similar outcomes with bortezomib compared with FGFR3-negative patients.
  
  
  CONCLUSIONS
  Baseline clinical variables and selective immunohistochemical markers expressed by patients may be used effectively to identify patients that are most likely to achieve a meaningful clinical response to bortezomib salvage therapy.
authors.affiliation: Clinical Haematology/Bone Marrow Transplant Department, The Alfred Hospital, Commercial Road, Prahran, Melbourne, Victoria, Australia 3181.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Dawson
authors.forename: Stephen S
authors.initials: SS
authors.lastname: Opat
authors.forename: Yamna
authors.initials: Y
authors.lastname: Taouk
authors.forename: Mark
authors.initials: M
authors.lastname: Donovan
authors.forename: Michele
authors.initials: M
authors.lastname: Zammit
authors.forename: Katherine
authors.initials: K
authors.lastname: Monaghan
authors.forename: Noemi
authors.initials: N
authors.lastname: Horvath
authors.forename: Andrew W
authors.initials: AW
authors.lastname: Roberts
authors.forename: H Miles
authors.initials: HM
authors.lastname: Prince
authors.forename: Mark
authors.initials: M
authors.lastname: Hertzberg
authors.forename: Catriona A
authors.initials: CA
authors.lastname: McLean
authors.forename: Andrew
authors.initials: A
authors.lastname: Spencer
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001897:Boronic Acids / Q000627:therapeutic use*; D000069286:Bortezomib; D002453:Cell Cycle; D015331:Cohort Studies; D019938:Cyclin D1 / Q000096:biosynthesis; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000096:biosynthesis; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods*; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy*; D011379:Prognosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D011719:Pyrazines / Q000627:therapeutic use*; D016896:Treatment Outcome; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis
chemical_list: D000970:Antineoplastic Agents; D001897:Boronic Acids; D019941:Cyclin-Dependent Kinase Inhibitor p16; D019253:Proto-Oncogene Proteins c-bcl-2; D011719:Pyrazines; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D019938:Cyclin D1; D000069286:Bortezomib