title: Efficacy and safety of pegylated liposomal Doxorubicin in combination with bortezomib for multiple myeloma: effects of adverse prognostic factors on outcome.
abstract: BACKGROUND
  Bortezomib with pegylated liposomal doxorubicin (PLD) is superior to bortezomib alone in the relapsed and/or refractory setting, based on the results of a randomized, parallel-group, open-label, multicenter phase III study. To identify patients who might most benefit from this new standard of care, we performed retrospective analyses evaluating the effects of clinically defined, high-risk features on the outcomes with this regimen.
  
  
  METHODS
  Patients received either bortezomib 1.3 mg/m2 on days 1, 4, 8, and 11 of an every-21-day cycle with PLD 30 mg/m2 on day 4 (n=324) or bortezomib alone (n=322). Four high- and low-risk subgroup categories were identified, including age≥65, ≥2 previous therapies, International Staging System stage II/III, and disease refractory to last previous therapy.
  
  
  RESULTS
  Compared with bortezomib alone, PLD plus bortezomib significantly prolonged the time to progression and duration of response in all of these subgroups. PLD plus bortezomib was well tolerated in all subgroups, and had a safety profile that was not affected by response to previous therapy.
  
  
  CONCLUSIONS
  Treatment of relapsed/refractory myeloma with the combination of PLD plus bortezomib provides better outcomes over bortezomib alone, even in the presence of high-risk prognostic factors. These results suggest that PLD plus bortezomib may represent an additional standard of care for this population of patients with multiple myeloma.
authors: Hematology Department, Hospital Clinic, IDIBAPS, Barcelona, Spain. jblade@clinic.ub.es
authors: Joan
authors: J
authors: Bladé
authors: Pieter
authors: P
authors: Sonneveld
authors: Jesús F
authors: JF
authors: San Miguel
authors: Heather J
authors: HJ
authors: Sutherland
authors: Roman
authors: R
authors: Hajek
authors: Arnon
authors: A
authors: Nagler
authors: Andrew
authors: A
authors: Spencer
authors: Tadeusz
authors: T
authors: Robak
authors: Keith C
authors: KC
authors: Lantz
authors: Sen H
authors: SH
authors: Zhuang
authors: Jean-Luc
authors: JL
authors: Harousseau
authors: Robert Z
authors: RZ
authors: Orlowski
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use*; D001897:Boronic Acids / Q000008:administration & dosage / Q000009:adverse effects; D000069286:Bortezomib; D018450:Disease Progression; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D005260:Female; D006801:Humans; D008297:Male; D009101:Multiple Myeloma / Q000188:drug therapy*; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000009:adverse effects; D011379:Prognosis; D011719:Pyrazines / Q000008:administration & dosage / Q000009:adverse effects; D012189:Retrospective Studies
chemical_list: D001897:Boronic Acids; D011719:Pyrazines; C506643:liposomal doxorubicin; D011092:Polyethylene Glycols; D000069286:Bortezomib; D004317:Doxorubicin