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Blood, 15 April 2008, Vol. 111, No. 8, pp. 3968-3977.
Prepublished online as a Blood First Edition Paper on February 1, 2008; DOI 10.1182/blood-2007-10-117457.


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REVIEW ARTICLE

Thalidomide for treatment of multiple myeloma: 10 years later

Antonio Palumbo1, Thierry Facon2, Pieter Sonneveld3, Joan Bladè4, Massimo Offidani5, Francesca Gay1, Philippe Moreau6, Anders Waage7, Andrew Spencer8, Heinz Ludwig9, Mario Boccadoro1, and Jean-Luc Harousseau10

1 Division of Hematology, University of Torino, Azienda Ospedaliera S Giovanni Battista, Torino, Italy; 2 University of Lille, Lille, France; 3 Erasmus Medical Center, Rotterdam, The Netherlands; 4 Hematology Department, Hospital Clinic, Institut d'Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS), Barcelona, Spain; 5 Hematology Clinic, University of Ancona, Ancona, Italy; 6 Hematology Department, University Hospital, Nantes, France; 7 Department of Haematology, University Hospital Trondheim, Trondheim, Norway; 8 Clinical Haematology and BMT, The Alfred Hospital, Melbourne, Australia; 9 First Department of Medicine, Center for Oncology and Haematology, Wilhelminenspital, Vienna, Austria; and 10 Hôspital Hotel-Dieu, Nantes, France

Thalidomide, bortezomib, and lenalidomide have recently changed the treatment paradigm of myeloma. In young, newly diagnosed patients, the combination of thalidomide and dexamethasone has been widely used as induction treatment before autologous stem cell transplantation (ASCT). In 2 randomized studies, consolidation or maintenance with low-dose thalidomide has extended both progression-free and overall survival in patients who underwent ASCT at diagnosis. In elderly, newly diagnosed patients, 3 independent randomized studies have reported that the oral combination of melphalan and prednisone plus thalidomide (MPT) is better than the standard melphalan and prednisone (MP). These studies have shown better progression-free survival, and 2 have shown improved overall survival for patients assigned to MPT. In refractory-relapsed disease, combinations including thalidomide with dexamethasone, melphalan, doxorubicin, or cyclophosphamide have been extensively investigated. The risks of side effects are greater when thalidomide is used in combination with other drugs. Thromboembolism and peripheral neuropathy are the major concern. The introduction of anticoagulant prophylaxis has reduced the rate of thromboembolism to less than 10%. Immediate thalidomide dose reduction or discontinuation when paresthesia is complicated by pain or motor deficit has decreased the severity of neuropathy. Future studies will define the most effective or the best sequence of combinations which could improve life expectancy.


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