Combined pegylated liposomal doxorubicin and bortezomib is highly effective in patients with recurrent or refractory multiple myeloma who received prior thalidomide/lenalidomide therapy

Cancer. 2008 Apr 1;112(7):1529-37. doi: 10.1002/cncr.23326.


Background: Recently, the authors reported improved time to disease progression (TTP) with a combination of pegylated liposomal doxorubicin (PLD) and bortezomib compared with bortezomib alone in a phase 3 randomized trial in patients with recurrent/refractory multiple myeloma (MM). In the current analysis, they determined 1) the efficacy of PLD plus bortezomib versus bortezomib alone in patients with MM who had failed on prior thalidomide/lenalidomide (immunomodulatory drug [IMiD]) treatment and 2) the efficacy and safety profile of PLD plus bortezomib in IMiD-exposed and IMiD-naive patients.

Methods: This prespecified analysis included 646 patients who were randomized to receive either PLD with bortezomib (n=324; 194 IMiD-naive patients and 130 IMiD-exposed patients) or bortezomib alone (n=322; 184 IMiD-naive patients and 138 IMiD-exposed patients). The primary efficacy endpoint was TTP, and secondary endpoints included overall survival, response rate, and safety.

Results: The median TTP was significantly longer with PLD plus bortezomib compared with bortezomib alone in IMiD-exposed patients (270 days vs 205 days). No statistical difference was noted with respect to TTP between IMiD-naive (295 days) versus IMiD-exposed (270 days) subgroups who received PLD plus bortezomib. A sustained trend favoring combination therapy was observed in analyses of overall survival. In patients who achieved a response, the response duration was comparable for IMiD-naive patients and IMiD-exposed patients in the combination treatment group and lasted a median of 310 days and 319 days, respectively. The incidence of grade 3/4 adverse events was similar with PLD plus bortezomib regardless of prior IMiD exposure.

Conclusions: A significantly prolonged TTP was observed with combined PLD plus bortezomib combination therapy compared with bortezomib alone despite prior IMiD exposure. For the combination treatment arm in the IMiD-naive and IMiD-exposed subgroups, TTP was comparable. Similarly, the safety profile of the PLD plus bortezomib combination was unaltered by prior IMiD exposure.

Trial registration: NCT00103506.

Publication types

  • Clinical Trial, Phase III
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • 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
  • Female
  • Humans
  • Lenalidomide
  • Male
  • Middle Aged
  • Multiple Myeloma / complications
  • Multiple Myeloma / drug therapy*
  • Neoplasm Recurrence, Local / diagnosis
  • Neoplasm Recurrence, Local / drug therapy*
  • Neoplasm Recurrence, Local / etiology
  • Polyethylene Glycols / administration & dosage
  • Pyrazines / administration & dosage
  • Salvage Therapy
  • Survival Rate
  • Thalidomide / administration & dosage
  • Thalidomide / analogs & derivatives


  • Boronic Acids
  • Pyrazines
  • liposomal doxorubicin
  • Polyethylene Glycols
  • Thalidomide
  • Bortezomib
  • Doxorubicin
  • Lenalidomide

Associated data