Combined pegylated liposomal doxorubicin and bortezomib is highly effective in patients with recurrent or refractory multiple myeloma who received prior thalidomide/lenalidomide therapy
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, R Bezares, V Labanca, S Orlando, J Sanchez Avalos, H Herrmann, M Hertzberg, N Horvath, D Joshua, D Ma, A Roberts, C Ward, J Drach, H Gisslinger, R Greil, E Gunsilius, W Linkesch, H Ludwig, J Thaler, M Delforge, C Doyen, A Janssens, L Noens, R Schots, A Belch, R Delage, T Kouroukis, J Roy, H Sutherland, R Van der Jagt, V Scudla, I Spicka, M Attal, L Benboubker, P Casassus, M Divine, T Facon, C Haioun, C Hulin, M Hunault, M Michallet, M Boccadoro, G Castoldi, F Dammacco, R Foa, F Rodeghiero, D Ben-Yehuda, A Berrebi, I Hardan, M Mittelman, E Naperstek, B Roth, J Rowe, R Ruchlamer, O Shpilberg, A Winder, D Biesma, M Kersten, H Lokhorst, G Ossenkoppele, R Raymakers, C Segeren, E Vellenga, P Wijermans, S Wittebol, P Browett, A Dmoszynska, A Hellmann, W Jedrzejczak, J Kloczko, K Kuliczkowski, J De Lacerda, G Esteves, A Teixeira, P Teixeira, K Abdulkadyrov, J Alexeeva, M Biakhov, N Domnikova, Y Dunaev, A Golenkov, N Khuageva, A Loginov, E Osmanov, V Pavlov, O Rukavitsyn, O Samoilova, A Suvorov, M Ming Fook, G Yeow, A Alegre, L Garcia, J Lahuerta, J San Miguel, G Cohen, P Jacobs, V Louw, N Novitzky, M Patel, B Rapoport, P Ruff, A Rahemtulla, K Yong, C Singer, K Yong, R Ansari, J Berdeja, B Berryman, A Brown, F Butler, V Caggiano, J Catlett, P Dainer, S Del Prete, H Fung, L Fehrenbacher, S Ferguson, R Frank, C Fu, J Glass, J Gurtler, J Hainsworth, W Hanna, G Harrer, D Henry, C Holladay, D Howard, R Jacobson, P Jaroonwanichkul, K Karamlou, D Khaira, K Lee, S Limentani, M Moezi, A Mohrbacher, V Morrison, D Patel, J Phelan, H Richter, R Rifkin, D Rizzieri, M Saleh, G Schiller, R Shadduck, D Shiba, D Siegel, M Silverman, P Swanson, J Tuscano, R Vescio, T Walters, J Wolf, S Zrada, 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, R Bezares, V Labanca, S Orlando, J Sanchez Avalos, H Herrmann, M Hertzberg, N Horvath, D Joshua, D Ma, A Roberts, C Ward, J Drach, H Gisslinger, R Greil, E Gunsilius, W Linkesch, H Ludwig, J Thaler, M Delforge, C Doyen, A Janssens, L Noens, R Schots, A Belch, R Delage, T Kouroukis, J Roy, H Sutherland, R Van der Jagt, V Scudla, I Spicka, M Attal, L Benboubker, P Casassus, M Divine, T Facon, C Haioun, C Hulin, M Hunault, M Michallet, M Boccadoro, G Castoldi, F Dammacco, R Foa, F Rodeghiero, D Ben-Yehuda, A Berrebi, I Hardan, M Mittelman, E Naperstek, B Roth, J Rowe, R Ruchlamer, O Shpilberg, A Winder, D Biesma, M Kersten, H Lokhorst, G Ossenkoppele, R Raymakers, C Segeren, E Vellenga, P Wijermans, S Wittebol, P Browett, A Dmoszynska, A Hellmann, W Jedrzejczak, J Kloczko, K Kuliczkowski, J De Lacerda, G Esteves, A Teixeira, P Teixeira, K Abdulkadyrov, J Alexeeva, M Biakhov, N Domnikova, Y Dunaev, A Golenkov, N Khuageva, A Loginov, E Osmanov, V Pavlov, O Rukavitsyn, O Samoilova, A Suvorov, M Ming Fook, G Yeow, A Alegre, L Garcia, J Lahuerta, J San Miguel, G Cohen, P Jacobs, V Louw, N Novitzky, M Patel, B Rapoport, P Ruff, A Rahemtulla, K Yong, C Singer, K Yong, R Ansari, J Berdeja, B Berryman, A Brown, F Butler, V Caggiano, J Catlett, P Dainer, S Del Prete, H Fung, L Fehrenbacher, S Ferguson, R Frank, C Fu, J Glass, J Gurtler, J Hainsworth, W Hanna, G Harrer, D Henry, C Holladay, D Howard, R Jacobson, P Jaroonwanichkul, K Karamlou, D Khaira, K Lee, S Limentani, M Moezi, A Mohrbacher, V Morrison, D Patel, J Phelan, H Richter, R Rifkin, D Rizzieri, M Saleh, G Schiller, R Shadduck, D Shiba, D Siegel, M Silverman, P Swanson, J Tuscano, R Vescio, T Walters, J Wolf, S Zrada
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.
Trial registration: ClinicalTrials.gov NCT00103506.
Source: PubMed