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

Cancer. 2011 Aug 15;117(16):3758-62. doi: 10.1002/cncr.25937. Epub 2011 Feb 15.

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.

Publication types

  • Clinical Trial, Phase III
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Boronic Acids / administration & dosage*
  • Bortezomib
  • Disease Progression
  • Doxorubicin / administration & dosage
  • Doxorubicin / analogs & derivatives*
  • Humans
  • Multiple Myeloma / drug therapy
  • Multiple Myeloma / metabolism*
  • Myeloma Proteins / metabolism*
  • Polyethylene Glycols / administration & dosage*
  • Pyrazines / administration & dosage*
  • Recurrence

Substances

  • Boronic Acids
  • Myeloma Proteins
  • Pyrazines
  • liposomal doxorubicin
  • multiple myeloma M-proteins
  • Polyethylene Glycols
  • Bortezomib
  • Doxorubicin