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

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. Cancer 2008. © 2008 American Cancer Society. Combined treatment with pegylated liposomal doxorubicin and bortezomib significantly prolonged the time to disease progression compared with bortezomib alone in patients with recurrent or refractory multiple myeloma despite prior exposure to the thalidomide/lenalidomide (immunomodulatory drug [IMiD]) therapy. The safety profile of this combination was una