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

Abstract

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.

• Authors: Pieter Sonneveld, Roman Hajek, Arnon Nagler, Andrew Spencer, Joan Bladé, Tadeusz Robak, Sen H Zhuang, Jean-Luc Harousseau, Robert Z Orlowski, DOXIL-MMY-3001 Study Investigators
• Journal: Cancer (Cancer) Vol. 112 Issue 7 Pg. 1529-37 (Apr 01 2008) ISSN: 0008-543X [Print] United States
• PMID: 18300257 (Publication Type: Clinical Trial, Phase III, Journal Article, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Boronic Acids (administration & dosage)
• Bortezomib
• Disease Progression
• Doxorubicin (administration & dosage, analogs & derivatives)
• Female
• Humans
• Lenalidomide
• Male
• Middle Aged
• Multiple Myeloma (complications, drug therapy)
• Neoplasm Recurrence, Local (diagnosis, drug therapy, etiology)
• Polyethylene Glycols (administration & dosage)
• Pyrazines (administration & dosage)
• Salvage Therapy
• Survival Rate
• Thalidomide (administration & dosage, analogs & derivatives)