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

Authors

  • Pieter Sonneveld MD, PhD,

    Corresponding author
    1. Department of Hematology, Erasmus Medical Center, Rotterdam, Netherlands
    • Department of Hematology, Erasmus MC, Center Location, Room L-439, P.O. Box 2040, 3000 CA Rotterdam, Netherlands
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    • Dr. Sonneveld has served on the Advisory Board of Jansson Cilag.

    • Fax: (011) 31 10 463 5814

  • Roman Hajek MD, PhD,

    1. Department of Internal Medicine and Hematooncology, University Hospital and Faculty of Medicine, Masaryk University, Brno, Czech Republic
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    • Dr. Hajek has received lecture honoraria.

  • Arnon Nagler MD, MSc,

    1. Department of Hematology, Bone Marrow Transplantation and Cord Blood Bank, Chaim Sheba Medical Center, Tel Hashomer, Israel
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  • Andrew Spencer DM,

    1. Malignant Haematology & Stem Cell Transplantation Service, Alfred Hospital, Melbourne, Victoria, Australia
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  • Joan Bladé MD,

    1. Hematology Department, Hospital Clinic I Provincial, Barcelona, Spain
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  • Tadeusz Robak MD, PhD,

    1. Department of Hematology, Medical University of Lodz, Lodz, Poland
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    • Dr. Robak has received a research grant from Johnson&Johnson.

  • Sen H. Zhuang MD, PhD,

    1. Ortho Biotech Oncology Research & Development, Johnson & Johnson Pharmaceutical Research and Development, L.L.C., Raritan, New Jersey
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    • Dr. Zhuang is employed by Johnson&Johnson PRD.

  • Jean-Luc Harousseau MD,

    1. Department of Hematology, University Hospital Hotel-Dieu, Nantes, France
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    • Dr. Harousseau has acted as a member of the Speakers′ Bureau for Ortho Biotech and the Advisory Boards of Millennium Pharmaceuticals and Ortho Biotech.

  • Robert Z. Orlowski MD, PhD,

    1. Departments of Lymphoma/Myeloma & Experimental Therapeutics, The University of Texas M. D. Anderson Cancer Center, Houston, Texas
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    • Dr. Orlowski, a Leukemia and Lymphoma Society Mansbach Foundation Scholar in Clinical Research, was supported by the Leukemia and Lymphoma Society (Grant 6096-07), the Multiple Myeloma Research Foundation, and the National Cancer Institute (Grant RO1 CA102278).

    • Dr. Orlowski has acted as a member of the Advisory Boards for Millennium Pharmaceuticals and Ortho Biotech.

  • for the DOXIL-MMY-3001 Study Investigators

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    • In addition to the authors, the following investigators (listed in alphabetical order) participated in the DOXIL-MMY-3001 study: Argentina: R. Bezares (Buenos Aires), V. Labanca (Mendoza), S. Orlando (Buenos Aires), and J. Sanchez Avalos (Buenos Aires); Australia: H. Herrmann (Perth), M. Hertzberg (New South Wales), N. Horvath (Adelaide), D. Joshua (New South Wales), D. Ma (New South Wales), A. Roberts (Victoria), and C. Ward (St. Leonards); Austria: J. Drach (Vienna), H. Gisslinger (Vienna), R. Greil (Salzburg), E. Gunsilius (Innsbruck), W. Linkesch (Graz), H. Ludwig (Vienna), and J. Thaler (Weis); Belgium: M. Delforge (Leuven), C. Doyen (Yvoir), A. Janssens (Gent), L. Noens (Gent), and R. Schots (Brussels); Canada: A. Belch (Edmonton), R. Delage (Quebec), T. Kouroukis (Hamilton), J. Roy (Quebec), H. Sutherland (Vancouver), and R. Van der Jagt (Ontario); Czech Republic: V. Scudla (Olomouc) and I. Spicka (Prague); France: M. Attal (Toulouse), L. Benboubker (Tours), P. Casassus (Bobigny), M. Divine (Creteil), T. Facon (Lille), C. Haioun (Creteil), C. Hulin (Nancy), M. Hunault (Angers), and M. Michallet (Lyons); Italy: M. Boccadoro (Torino), G. Castoldi (Ferrara), F. Dammacco (Bari), R. Foa (Rome), and F. Rodeghiero (Vicenza); Israel: D. Ben-Yehuda (Jerusalem), A. Berrebi (Rehovot), I. Hardan (Tel Hashomer), M. Mittelman (Tel Aviv), E. Naperstek (Tel Aviv), B. Roth (Jerusalem), J. Rowe (Haifa), R. Ruchlamer (Jerusalem), O. Shpilberg (Petach Tikva), and A. Winder (Holon); Netherlands: D. Biesma (Koekoekslaan), M. Kersten (Amsterdam), H. Lokhorst (Utrecht), G. Ossenkoppele (Amsterdam), R. Raymakers (Nijmegen), C. Segeren (Delft), E. Vellenga (Groningen), P. Wijermans (Den Haag), and S. Wittebol (Amersfoort); New Zealand: P. Browett (Auckland); Poland: A. Dmoszynska (Lublin), A. Hellmann (Gdansk), W. Jedrzejczak (Warsaw), J. Kloczko (Bialystok), and K. Kuliczkowski (Wroclaw); Portugal: J. De Lacerda (Lisboa), G. Esteves (Lisbon), A. Teixeira (Coimbra), and P. Teixeira (Porto); Russia: K. Abdulkadyrov (St. Petersburg), J. Alexeeva (St. Petersburg), M. Biakhov (Moscow), N. Domnikova (Novosibirsk), Y. Dunaev (Arkhangelsk), A. Golenkov (Moscow), N. Khuageva (Moscow), A. Loginov (Ekaterinburg), E. Osmanov (Moscow), V. Pavlov (Obninsk), O. Rukavitsyn (Moscow), O. Samoilova (Novgorod), and A. Suvorov (Izhevsk); Singapore: M. Ming Fook (Singapore) and G. Yeow (Singapore); Spain: A. Alegre (Madrid), L. Garcia (Madrid), J. Lahuerta (Madrid), and J. San Miguel (Salamanca); South Africa: G. Cohen (Pretoria), P. Jacobs (Cape Town), V. Louw (Bloemfontein), N. Novitzky (Cape Town), M. Patel (Johannesburg), B. Rapoport (Johannesburg), and P. Ruff (Parktown); United Kingdom: A. Rahemtulla (London), K. Yong (London), C. Singer (Bath), and K. Yong (London); United States: R. Ansari (South Bend, Ind), J. Berdeja (Loma Linda, Calif), B. Berryman (Dallas, Tex), A. Brown (New Orleans, La), F. Butler (Parkdale Place, Ind), V. Caggiano (Sacramento, Calif), J. Catlett (Washington, DC), P. Dainer (Augusta, Ga), S. Del Prete (Stamford, Conn), H. Fung (Chicago, Ill), L. Fehrenbacher (Vallejo, Calif), S. Ferguson (Hoover, Ala), R. Frank (Norwalk, Conn), C. Fu (Weston, Fla), J. Glass (Shreveport, La), J. Gurtler (Nashville, Tenn), J. Hainsworth (Nashville, Tenn), W. Hanna (Knoxville, Tenn), G. Harrer (Great Falls, Mont), D. Henry (Philadelphia, Pa), C. Holladay (Charleston, SC), D. Howard (Charleston, SC), R. Jacobson (West Palm Beach, Fla), P. Jaroonwanichkul (Branson, Mo), K. Karamlou (Portland, Ore), D. Khaira (Surprise, Ariz), K. Lee (Miami, Fla), S. Limentani (Charlotte, NC), M. Moezi (Jacksonville, Fla), A. Mohrbacher (Los Angeles, Calif), V. Morrison (Minneapolis, Minn), D. Patel (New Hyde Park, NY), J. Phelan (Rochester, NY), H. Richter (Boca Raton, Fla), R. Rifkin (Denver, Colo), D. Rizzieri (Durham, NC), M. Saleh (Tucker, Ga), G. Schiller (Los Angeles, Calif), R. Shadduck (Pittsburgh, Pa), D. Shiba (Modesto, Calif), D. Siegel (Hackensack, NJ), M. Silverman (Iowa City, Iowa), P. Swanson (Port St. Lucie, Fla), J. Tuscano (Sacramento, Calif), R. Vescio (Los Angeles, Calif), T. Walters (Boise, Idaho), J. Wolf (Berkeley, Calif), and S. Zrada (Cherry Hill, NJ).


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. Cancer 2008. © 2008 American Cancer Society.

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