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Supplementary Table 1. FDA indications and NCCN recommendations for MM therapies discussed in this review Agent FDA indication NCCN recommendations Indicated for the treatment of patients with MM Induction therapy prior to transplant (VCD, VD, VD+Doxil, PAD, RVD, VTD), Proteasome inhibitors Bortezomib frontline therapy in patients ineligible for transplant (VMP, VD), and salvage therapy (V, VD, VCD, RVD, V+Doxil) Carfilzomib N/A N/A Marizomib N/A N/A Indicated in combination with dexamethasone for the Induction therapy prior to transplant (VTD, TD), frontline therapy in patients treatment of patients with newly diagnosed MM ineligible for transplant (TD, MPT), maintenance (alone or in combination with Immunomodulatory drugs Thalidomide prednisone), and salvage therapy (DT-PACE, T, TD) Lenalidomide Indicated in combination with dexamethasone for the Induction therapy prior to transplant (RD, RVD), frontline therapy in patients treatment of patients with MM who have received at ineligible for transplant (Rd, MPR), maintenance (R), and salvage therapy (R, RD, least one prior therapy RCD, RVD) N/A N/A Indicated in acute leukemia Induction therapy prior to transplant (DVD), and salvage therapy (C-VAD) Indicated in metastatic testicular and ovarian tumors Salvage therapy (DT-PACE) Pomalidomide Vinca alkaloids Vincristine Platinum-based agents Cisplatin and advanced bladder cancer C-VAD, cyclophosphamide, vincristine, doxorubicin, dexamethasone; Doxil, liposomal doxorubicin; DT-PACE, dexamethasone, thalidomide, cisplatin, doxorubicin, cyclophosphamide, etoposide); DVD, liposomal doxorubicin, vincristine, dexamethasone; MPR, melphalan, prednisone, lenalidomide; MPT, melphalan, prednisone, thalidomide; N/A, not applicable; PAD, bortezomib, doxorubicin, dexamethasone; R, lenalidomide; RCD, lenalidomide, cyclophosphamide, dexamethasone; RD/d, lenalidomide, high-/low-dose dexamethasone; RVD, lenalidomide, bortezomib, dexamethasone; T, thalidomide; TD, thalidomide, dexamethasone; V, bortezomib; VCD, bortezomib, cyclophosphamide, dexamethasone; VD, bortezomib, dexamethasone; VMP, bortezomib, melphalan, prednisone; VTD, bortezomib, thalidomide, dexamethasone Supplementary Table 2. Potential supplemental interventions used at the Dana-Farber Cancer Institute Supplement Dose Multi B-complex vitamins Approximately 50 mg/day with B1, B6, B12, folic acid, and other B6, not to exceed 100 mg/day. Folic acid 1 mg/day Vitamin E 400 IU/day Vitamin D 400–800 IU/day Magnesium 250 mg twice-daily (over-the-counter); or 400 mg/day by prescription, with frequency dependent on serum magnesium levels Potassium As provided by treating physician or increased intake of foods rich in potassium (such as bananas, oranges, potatoes) Acetyl-L-carnitine 500 mg twice-daily with food; can take up to 2000 mg/day Alpha-lipoic acid 300 –1000 mg/day with food Glutamine 1 g up to three times daily with food Supplements should be taken with food unless otherwise indicated. It is currently advised that patients do not take supplements on days of bortezomib infusion and all supplements must be discussed with and approved by the treating physicians concerned. The effectiveness of the use of the above supplemental interventions is not proven in prospective studies. Supplementary acknowledgments – The International Myeloma Working Group Niels Abildgaard, Syddansk Universitet, Odense, Denmark Rafat Abonour, Indiana University School of Medicine, Indianapolis, IN, USA Ray Alexanian, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA Melissa Alsina, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA Kenneth C. Anderson, Dana-Farber Cancer Institute, Boston, MA, USA Michel Attal, Purpan Hospital, Toulouse, France Hervé Avet-Loiseau, Institute de Biologie, Nantes, France Ashraf Badros, University of Maryland, Baltimore, MD, USA Dalsu Baris, National Cancer Institute, Bethesda, MD, USA Bart Barlogie, Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR, USA Régis Bataille, Institute de Biologie, Nantes, France Meral Beksaç, Ankara University, Ankara, Turkey Andrew Belch, Cross Cancer Institute, Alberta, Canada Dina Ben-Yehuda, Hadassah University Hospital, Hadassah, Israel Bill Bensinger, Fred Hutchinson Cancer Research Center, Seattle, WA, USA P. Leif Bergsagel, Mayo Clinic Scottsdale, Scottsdale, AZ, USA Jenny Bird, Bristol Haematology and Oncology Center, Bristol, UK Joan Bladé, Hospital Clinic, University of Barcelona, Barcelona, Spain Mario Boccadoro, University of Torino, Torino, Italy Michele Cavo, Seràgnoli Institute of Hematology, Bologna University School of Medicine, Bologna, Italy Asher Chanan-Khan, Roswell Park Cancer Institute, Buffalo, NY, USA Wen Ming Chen, MM Research Center of Beijing, Beijing, China Marta Chesi, Mayo Clinic Scottsdale, Scottsdale, AZ, USA Tony Child, Leeds General Hospital, Leeds, UK James Chim, Department of Medicine, Queen Mary Hospital, Hong Kong Wee-Joo Chng, Department of Haematology and Oncology, National University Health System, Singapore Raymond Comenzo, Tufts Medical Center, Boston, MA, USA John Crowley, Cancer Research and Biostatistics, Seattle, WA, USA William Dalton, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA Faith Davies, Royal Marsden Hospital, London, UK Cármino de Souza, Univeridade de Campinas, Caminas, Brazil Michel Delforge, University Hospital Leuven, Leuven, Belgium Meletios Dimopoulos, University of Athens School of Medicine, Athens, Greece Angela Dispenzieri, Mayo Clinic, Rochester, MN, USA Johannes Drach, University of Vienna, Vienna, Austria Matthew Drake, Mayo Clinic, Rochester, MN, USA Brian G.M. Durie, Cedars-Sinai Samuel Oschin Cancer Center, Los Angeles, CA, USA; Aptium Oncology Inc., Los Angeles, CA, USA Hermann Einsele, Universitätsklinik Würzburg, Würzburg, Germany Theirry Facon, Centre Hospitalier Regional Universitaire de Lille, Lille, France Dorotea Fantl, Socieded Argentinade Hematolgia, Buenos Aires, Argentina Jean-Paul Fermand, Hopitaux de Paris, Paris, France Rafael Fonseca, Mayo Clinic Scottsdale, Scottsdale, AZ, USA Gösta Gahrton, Karolinska Institute for Medicine, Huddinge, Sweden Ramón García-Sanz, University Hospital of Salamanca, Salamanca, Spain Christina Gasparetto, Duke University Medical Center, Durham, NC, USA Morie Gertz, Mayo Clinic, Rochester, MN, USA John Gibson, Royal Prince Alfred Hospital, Sydney, Australia Sergio Giralt, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA Hartmut Goldschmidt, University Hospital Heidelberg, Heidelberg, Germany Philip Greipp, Mayo Clinic, Rochester, MN, USA Roman Hajek, Brno University, Brno, Czech Republic Izhar Hardan, Tel Aviv University, Tel Aviv, Israel Parameswaran Hari, Medical College of Wisconsin, Milwaukee, WI, USA Hiroyuki Hata, Kumamoto University Hospital, Kumamoto, Japan Yutaka Hattori, Keio University School of Medicine, Tokyo, Japan Tom Heffner, Winship Cancer Institute of Emory University, Atlanta, GA, USA Joy Ho, Royal Prince Alfred Hospital, Sydney, Australia Vania Hungria, Clinica San Germano, Sao Paolo, Brazil Shinsuke Ida, Nagoya City University Medical School, Nagoya, Japan Peter Jacobs, Constantiaberg Medi-Clinic, Plumstead, South Africa Sundar Jagannath, Mt. Sinai Hospital, New York, NY, USA Hans Johnsen, Aalborg Hospital Science and Innovation Center, Aalborg, Denmark Hou Jian, Shanghai Chang Zheng Hospital, Shanghai, China Douglas Joshua, Royal Prince Alfred Hospital, Sydney, Australia Artur Jurczyszyn, The Myeloma Treatment Foundation, Poland Jonathan Kaufman, Winship Cancer Institute of Emory University, Atlanta, GA, USA Michio Kawano, Yamaguchi University, Ube, Japan Eva Kovacs, Cancer Immunology Research-Life, Birsfelden, Switzerland Amrita Krishnan, City of Hope, Duarte, CA, USA Nicolaus Kröger, University Hospital Hamburg, Hamburg, Germany Shaji Kumar, Division of Hematology, Mayo Clinic, Rochester, MN, USA Robert A. Kyle, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA Martha Lacy, Mayo Clinic, Rochester, MN, USA Juan José Lahuerta, Grupo Español di Mieloma, Hospital Universitario 12 de Octubre, Madrid, Spain Ola Landgren, National Cancer Institute, Bethesda, MD, USA Jacob Laubach, Dana-Farber Cancer Institute, Boston, MA, USA Jae Hoon Lee, Gachon University Gil Hospital, Incheon, Korea Xavier LeLeu, Hospital Huriez, CHRU Lille, France Suzanne Lentzsch, University of Pittsburgh, Pittsburgh, PA, USA Henk Lokhorst, University Medical Center Utrecht, Utrecht, The Netherlands Sagar Lonial, Winship Cancer Institute of Emory University, Atlanta, GA, USA Heinz Ludwig, Wilhelminenspital Der Stat Wien, Vienna, Austria Angelo Maiolino, Rua fonte da Saudade, Rio de Janeiro, Brazil María Mateos, Hospital Universitario Salamanca, CIC, IBMCC (USAL-CSIC), Salamanca, Spain Amitabha Mazumder, New York University School of Medicine, New York, NY, USA Jayesh Mehta, Northwestern University, Chicago, IL, USA Ulf-Henrik Mellqvist, Sahlgrenska University Hospital, Gothenburg, Sweden Giampaolo Merlini, University of Pavia, Pavia, Italy Joseph Mikhael, Mayo Clinic Scottsdale, Scottsdale, AZ, USA Philip McCarthy, Roswell Park Cancer Center, Buffalo, NY, USA Philippe Moreau, University Hospital, Nantes, France Gareth Morgan, Royal Marsden Hospital, London, UK Hareth Nari, Karolinska University Hospital, Stockholm, Sweden Nikhil Munshi, Diane Farber Cancer Institute, Boston, MA, USA Ruben Niesvizky, Center of Excellence for Lymphoma and Myeloma, Weill Medical College of Cornell University, New York Presbyterian Hospital, New York, NY, USA Amara Nouel, Hospital Rutz y Paez, Bolivar, Venezuela Yana Novis, Hospital Sírio Libanês, Bela Vista, Brazil Robert Orlowski, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA Antonio Palumbo, University of Torino, Torino, Italy Santiago Pavlovsky, Fundaleu, Buenos Aires, Argentina Linda Pilarski, University of Alberta, Alberta, Canada Raymond Powles, Leukemia & Myeloma, Wimbledon, UK Noopur Raje, Massachusetts General Hospital, Boston, MA, USA S. Vincent Rajkumar, Mayo Clinic, Rochester, MN, USA Donna Reece, Princess Margaret Hospital, Toronto, Canada Tony Reiman, Saint John Regional Hospital, Saint John, New Brunswick, Canada Paul G. Richardson, Dana Farber Cancer Institute, Boston, MA, USA Angelina Rodríguez Morales, Bonco Metro Politano de Sangre, Caracas, Venezuela David Roodman, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA Laura Rosiñol, Hospital Clinic, Barcelona, Spain Stephen Russell, Mayo Clinic, Rochester, MN, USA Jesús San Miguel, Hospital Universitario Salamanca, CIC, IBMCC (USAL-CSIC), Salamanca, Spain Sabina Sevcikova, Masaryk University, Brno, Czech Republic Orhan Sezer, Universität Hamburg, Hamburg, Germany Jatin J. Shah, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA John Shaughnessy, Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR, USA Kazuyuki Shimizu, Nagoya City Midori General Hospital, Nagoya, Japan Chaim Shustik, McGill University, Montreal, Canada David Siegel, Hackensack Cancer Center, Hackensack, NJ, USA Seema Singhal, Northwestern University, Chicago, IL, USA Pieter Sonneveld, Erasmus MC, Rotterdam, The Netherlands Andrew Spencer, The Alfred Hospital, Melbourne, Australia Edward Stadtmauer, University of Pennsylvania, Philadelphia, PA, USA Keith Stewart, Mayo Clinic Scottsdale, Scottsdale, AZ, USA Evangelos Terpos, University of Athens School of Medicine, Athens, Greece Patrizia Tosi, Italian Cooperative Group, Istituto di Ematologia Seragnoli, Bologna, Italy Guido Tricot, Huntsman Cancer Institute, Salt Lake City, UT, USA Ingemar Turesson, SKANE University Hospital, Malmo, Sweden Saad Usmani, Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR, USA Ben Van Camp, Vrije Universiteit Brussels, Brussels, Belgium Brian Van Ness, University of Minnesota, Minneapolis, MN, USA Ivan Van Riet, Brussels Vrija University, Brussels, Belgium Isabelle Vande Broek, Vrije Universiteit Brussels, Brussels, Belgium Karin Vanderkerken, Vrije University Brussels VUB, Brussels, Belgium Robert Vescio, Cedars-Sinai Cancer Center, Los Angeles, CA, USA David Vesole, Hackensack Cancer Center, Hackensack, NJ, USA Peter Voorhees, University of North Carolina, Chapel Hill, NC, USA Anders Waage, NSMG, University Hospital, Trondheim, Norway Michael Wang, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA Donna Weber, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA Jan Westin, Sahlgrenska University Hospital, Gothenburg, Sweden Keith Wheatley, University of Birmingham, Birmingham, UK Elena Zamagni, University of Bologna, Bologna, Italy Jeffrey Zonder, Karmanos Cancer Institute, Detroit, MI, USA
