title: Rapid early monoclonal protein reduction after therapy with bortezomib or bortezomib and pegylated liposomal doxorubicin in relapsed/refractory myeloma is associated with a longer time to progression.
abstract: BACKGROUND
  A rapid and early monoclonal (M) protein response during initial therapy in patients with multiple myeloma had been identified as a predictor of superior long-term outcome in some--but not all--studies.
  
  
  METHODS
  To determine if the parameter of M protein reduction was of value in the relapsed and/or refractory setting, retrospective landmark analyses were performed at the end of cycles 2 and 4 of a phase 3 study, which randomized such patients to receive bortezomib alone or pegylated liposomal doxorubicin (PLD) with bortezomib.
  
  
  RESULTS
  Compared with a <25% reduction in M protein at the landmark time point, patients with a 50% to <75% reduction after cycle 2 had a significantly lower hazard ratio (HR) for time to progression (HR = 0.41; 95% confidence interval [CI], 0.26-0.64; P <.001), as did those with a ≥75% reduction (HR = 0.26; 95% CI, 0.15-0.45; P < .001). In all of these groups, PLD + bortezomib provided superior outcomes to bortezomib alone, and did so without an increase in the risk of adverse events overall and with a predictable toxicity profile.
  
  
  CONCLUSIONS
  These analyses supported the possibility that a robust early M protein response is a good prognostic factor for long-term outcome of myeloma patients with relapsed and/or refractory disease receiving bortezomib or PLD + bortezomib.
authors.affiliation: The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA. jjshah@mdanderson.org
authors.forename: Jatin
authors.initials: J
authors.lastname: Shah
authors.forename: Joan
authors.initials: J
authors.lastname: Bladé
authors.forename: Pieter
authors.initials: P
authors.lastname: Sonneveld
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Harousseau
authors.forename: Keith
authors.initials: K
authors.lastname: Lantz
authors.forename: Anil
authors.initials: A
authors.lastname: Londhe
authors.forename: Colin
authors.initials: C
authors.lastname: Lowery
authors.forename: Robert Z
authors.initials: RZ
authors.lastname: Orlowski
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001897:Boronic Acids / Q000008:administration & dosage*; D000069286:Bortezomib; D018450:Disease Progression; D004317:Doxorubicin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D006801:Humans; D009101:Multiple Myeloma / Q000188:drug therapy / Q000378:metabolism*; D009194:Myeloma Proteins / Q000378:metabolism*; D011092:Polyethylene Glycols / Q000008:administration & dosage*; D011719:Pyrazines / Q000008:administration & dosage*; D012008:Recurrence
chemical_list: D001897:Boronic Acids; D009194:Myeloma Proteins; D011719:Pyrazines; C506643:liposomal doxorubicin; C085016:multiple myeloma M-proteins; D011092:Polyethylene Glycols; D000069286:Bortezomib; D004317:Doxorubicin