The prognosis for patients multiple myeloma (MM) has improved substantially over the past decade with the development of new, more effective chemotherapeutic agents and regimens that possess a high level of anti-tumor activity. In spite of this important progress, however, nearly all MM patients ultimately relapse, even those who experience a complete response to initial therapy. Management of relapsed MM thus represents a vital aspect of the overall care for patients with MM and a critical area of ongoing scientific and clinical research. This comprehensive manuscript from the International Myeloma Working Group provides detailed recommendations on management of relapsed disease, with sections dedicated to diagnostic evaluation, determinants of therapy, and general approach to patients with specific disease characteristics. In addition, the manuscript provides a summary of evidence from clinical trials that have significantly impacted the field, including those evaluating conventional dose therapies, as well as both autologous and allogeneic stem cell transplantation. Specific recommendations are offered for management of first and second relapse, relapsed and refractory disease, and both autologous and allogeneic transplant. Finally, perspective is provided regarding new agents and promising directions in management of relapsed MM.
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We gratefully acknowledge the editorial support of Megan Hiserodt, Michelle Maglio and Lisa Paik in the preparation of this manuscript.
JL reports grants from Novartis, grants from Celgene, grants from Onyx, grants from Millennium, outside the submitted work. LG reports personal fees from BMS, personal fees from Amgen, outside the submitted work. AM has received honorarium from Millennium Pharmaceuticals in the last 36 months for advisory board. GG reports grants and personal fees from Celgene, personal fees from Fujimoto Pharmaceutical Company, Japan, outside the submitted work. OS reports personal fees from Amgen, personal fees from Celgene and personal fees from Janssen. PV reports personal fees and other from Celgene Corporation, personal fees from Millennium Pharmaceuticals: A Takeda Oncology Company, personal fees from Novartis, other from Array Biopharma, grants and other from Oncopeptides, grants from Onyx Pharmaceuticals, grants and personal fees from GlaxoSmithKline, grants from Janssen and grants from Acetylon Pharmaceuticals. XL has received honorarium from Celgene, Millennium, Amgen, Janssen, Novartis, BMS, TEVA, LeoPHARMA and Pierre Fabre. MS has received Speakers Fees from Celgene and Janssen. HL reports grants from Takeda, grants and personal fees from Celgene, personal fees from Amgen/Onyx, personal fees from Janssen-Cilag. U-HM reports honoraria from Novartis, Mundipharma, Celgene, Amgen and Janssen and participated in advisory boards for Amgen and Celgene. WJC has received Honorarium from Celgene, Janssen, Millennium Takeda, Novartis and Onyx. EZ has received honoraria from Celgene and Janssen. CSC has received honorarium from Celgene and Janssen. TR has received honoraria from Celgene and Janssen. DJ has served on the advisory boards for Celgene, Onyx and Janssen; DJ has received payment for services from Celgene and Janssen. MR reports grants and personal fees from Celgene, grants from Janssen and grants from Onyx. POG has received honoraria from Celgene, Janssen and Takeda. ET has received honoraria and research grants from Amgen and Janssen-Cilag; ET has received honoraria from Celgene and Roche. PM has received compensation/honoraria for participation in scientific advisory boards for Celgene, Janssen, Sanofi, Karyopharm, The Binding Site and Bristol Myers Squibb. MD has received honoraria from Celgene, Janssen, Onyx, Takeda and Novartis. PM has served on the advisory board for Janssen, Celgene, Takeda, Novartis and Amgen. RO has been funded by the NIH, and has also received research grants from Array Biopharma, Bristol-Myers Squibb, Celgene Corporation, Janssen, Millennium Pharmaceuticals and Spectrum Pharmaceuticals. In addition, he has served on scientific advisory boards with compensation for Abbott Laboratories, Amgen, Inc., Array Biopharma, Bristol-Myers Squibb, Celgene Corporation, Forma Therapeutics, Incyte, Janssen, Millennium Pharmaceuticals, on scientific advisory boards without compensation for Acetylon Pharmaceuticals, Inc. KCA has served on Advisory boards for Celgene, Millennium, Sanofi Aventis, Gilead and Bristol-Myers Squibb. KA is also the scientific founder of Acetylon and Oncopep. AP has received honoraria from Janssen, Celgene, Amgen, Millennium/Takeda and BMS. SK’s institution has received consulting fees from Merck, Millennium, Celgene, Sanofi/Genzyme and Onyx and grants from R01. SK has received payment for services from Sharp Healthcare. PGR has served on advisory boards for Celgene, Millennium, Johnson & Johnson, Novartis, Bristol-Myers Squibb and Onyx. JC, HEJ, AJ, LP, HE, JH, IT, AM, JW, JL, SK, VR and BD have nothing to disclose.
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