Supplementary Table 1. FDA indications and NCCN recommendations for MM therapies discussed in this review

Agent / FDA indication / NCCN recommendations
Proteasome inhibitors
Bortezomib / Indicated for the treatment of patients with MM / Induction therapy prior to transplant (VCD, VD, VD+Doxil, PAD, RVD, VTD), 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
Immunomodulatory drugs
Thalidomide / Indicated in combination with dexamethasone for the treatment of patients with newly diagnosed MM / Induction therapy prior to transplant (VTD, TD), frontline therapy in patients ineligible for transplant (TD, MPT), maintenance (alone or in combination with prednisone), and salvage therapy (DT-PACE, T, TD)
Lenalidomide / Indicated in combination with dexamethasone for the treatment of patients with MM who have received at least one prior therapy / Induction therapy prior to transplant (RD, RVD), frontline therapy in patients ineligible for transplant (Rd, MPR), maintenance (R), and salvage therapy (R, RD, RCD, RVD)
Pomalidomide / N/A / N/A
Vinca alkaloids
Vincristine / Indicated in acute leukemia / Induction therapy prior to transplant (DVD), and salvage therapy (C-VAD)
Platinum-based agents
Cisplatin / Indicated in metastatic testicular and ovarian tumors and advanced bladder cancer / Salvage therapy (DT-PACE)

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 TexasM.D.AndersonCancerCenter, Houston, TX, USA

Melissa Alsina, H. LeeMoffittCancerCenter 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, FredHutchinsonCancerResearchCenter, Seattle, WA, USA

P. Leif Bergsagel, Mayo Clinic Scottsdale, Scottsdale, AZ, USA

Jenny Bird, Bristol Haematology and OncologyCenter, Bristol, UK

Joan Bladé, Hospital Clinic,University of Barcelona,Barcelona, Spain

Mario Boccadoro, University of Torino, Torino, Italy

Michele Cavo, Seràgnoli Institute of Hematology, BolognaUniversitySchool 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, LeedsGeneralHospital, Leeds, UK

James Chim, Department of Medicine, QueenMaryHospital, Hong Kong

Wee-Joo Chng, Department of Haematology and Oncology, NationalUniversity Health System,Singapore

Raymond Comenzo, Tufts Medical Center, Boston, MA, USA

John Crowley, Cancer Research and Biostatistics, Seattle, WA, USA

William Dalton, H. LeeMoffittCancerCenter and Research Institute, Tampa, FL, USA

Faith Davies, RoyalMarsdenHospital, London, UK

Cármino de Souza, Univeridade de Campinas, Caminas, Brazil

Michel Delforge, UniversityHospitalLeuven, Leuven, Belgium

Meletios Dimopoulos, University of AthensSchool 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-SinaiSamuelOschinCancerCenter, 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 PrinceAlfredHospital, Sydney, Australia

Sergio Giralt, The University of TexasM.D.AndersonCancerCenter, Houston, TX, USA

Hartmut Goldschmidt, University Hospital Heidelberg, Heidelberg, Germany

Philip Greipp, Mayo Clinic, Rochester, MN, USA

Roman Hajek, BrnoUniversity, Brno, Czech Republic

Izhar Hardan, TelAvivUniversity, Tel Aviv, Israel

Parameswaran Hari, Medical College of Wisconsin, Milwaukee, WI, USA

Hiroyuki Hata, KumamotoUniversityHospital, Kumamoto, Japan

Yutaka Hattori, KeioUniversitySchool of Medicine, Tokyo, Japan

Tom Heffner, Winship Cancer Institute of EmoryUniversity, Atlanta, GA, USA

Joy Ho, Royal PrinceAlfredHospital, Sydney, Australia

Vania Hungria, Clinica San Germano, Sao Paolo, Brazil

Shinsuke Ida, NagoyaCityUniversityMedicalSchool, Nagoya, Japan

Peter Jacobs, Constantiaberg Medi-Clinic, Plumstead, South Africa

Sundar Jagannath, Mt. Sinai Hospital, New York, NY, USA

Hans Johnsen, AalborgHospital Science and InnovationCenter, Aalborg, Denmark

Hou Jian, ShanghaiChangZhengHospital, Shanghai, China

Douglas Joshua, Royal PrinceAlfredHospital, Sydney, Australia

Artur Jurczyszyn, The Myeloma Treatment Foundation, Poland

Jonathan Kaufman, Winship Cancer Institute of EmoryUniversity, Atlanta, GA, USA

Michio Kawano, YamaguchiUniversity, 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 CenterUtrecht, 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