@article{a63f6b8ecfef49b7a0c84811a69e57f2,
title = "New drugs and novel mechanisms of action in multiple myeloma in 2013: A report from the International Myeloma Working Group (IMWG)",
abstract = "Treatment in medical oncology is gradually shifting from the use of nonspecific chemotherapeutic agents toward an era of novel targeted therapy in which drugs and their combinations target specific aspects of the biology of tumor cells. Multiple myeloma (MM) has become one of the best examples in this regard, reflected in the identification of new pathogenic mechanisms, together with the development of novel drugs that are being explored from the preclinical setting to the early phases of clinical development. We review the biological rationale for the use of the most important new agents for treating MM and summarize their clinical activity in an increasingly busy field. First, we discuss data from already approved and active agents (including second- and third-generation proteasome inhibitors (PIs), immunomodulatory agents and alkylators). Next, we focus on agents with novel mechanisms of action, such as monoclonal antibodies (MoAbs), cell cycle-specific drugs, deacetylase inhibitors, agents acting on the unfolded protein response, signaling transduction pathway inhibitors and kinase inhibitors. Among this plethora of new agents or mechanisms, some are specially promising: anti-CD38 MoAb, such as daratumumab, are the first antibodies with clinical activity as single agents in MM. Moreover, the kinesin spindle protein inhibitor Arry-520 is effective in monotherapy as well as in combination with dexamethasone in heavily pretreated patients. Immunotherapy against MM is also being explored, and probably the most attractive example of this approach is the combination of the anti-CS1 MoAb elotuzumab with lenalidomide and dexamethasone, which has produced exciting results in the relapsed/refractory setting.",
keywords = "Multiple myeloma, New drugs, Phase I clinical trials, Targeted agents",
author = "Ocio, {E. M.} and Richardson, {P. G.} and Rajkumar, {S. V.} and A. Palumbo and Mateos, {M. V.} and R. Orlowski and S. Kumar and S. Usmani and D. Roodman and R. Niesvizky and H. Einsele and Anderson, {K. C.} and Dimopoulos, {M. A.} and H. Avet-Loiseau and Mellqvist, {U. H.} and I. Turesson and G. Merlini and R. Schots and P. Mccarthy and L. Bergsagel and Chim, {C. S.} and Lahuerta, {J. J.} and J. Shah and A. Reiman and J. Mikhael and S. Zweegman and S. Lonial and R. Comenzo and Chng, {W. J.} and P. Moreau and P. Sonneveld and H. Ludwig and Durie, {B. G.M.} and Miguel, {J. F.S.}",
note = "Funding Information: 1Department of Hematology, University Hospital and Cancer Research Center, University of Salamanca-IBSAL, IBMCC (USAL-CSIC), Salamanca, Spain; 2Department of Medicine, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA; 3Department of Hematology, Mayo Clinic, Rochester, MN, USA; 4Department of Hematology, University of Torino, Torino, Italy; 5Department of Lymphoma/Myeloma, MD Anderson Cancer Center, Houston, TX, USA; 6M.I.R.T. UAMS, Little Rock, AR, USA; 7Director of Hematology/ Oncology, Indiana University, Indianapolis, IN, USA; 8Department of Hematology, Weill Cornell Medical College, New York, NY, USA; 9Department of Internal Medicine, University of Wurzburg, Wurzburg, Germany; 10School of Medicine, University of Athens, Athens, Greece; 11Department of Hematology, University of Toulouse, Toulouse, France; 12Department of Medicine, Section of Hematology, Sahlgrenska University Hospital, Gothenburg, Sweden; 13Department of Medicine, Section of Hematology, Skane University Hospital, Malmo, Sweden; 14Department of Molecular Medicine, Univeristy of Pavia, Pavia, Italy; 15Department of Clinical Hematology and Stem Cell Laboratory, University Ziekenhuis, Brussels, Belgium; 16Department of Medicine, Roswell Park Cancer Institute, Buffalo, NY, USA; 17Division of Hematology and Oncology, Mayo Clinic, Scottsdale, AZ, USA; 18Department of Hematology, Queen Mary Hospital, Hong Kong; 19Department of Hematology, Hospital Universitario 12 de Octubre, Madrid, Spain; 20Department of Oncology, University of New Brunswick, Saint John Regional Hospital, St John, NB, Canada; 21Department of Hematology, VU University Medical Center, Amsterdam, The Netherlands; 22Department of Hematology and Medical Oncology, Shanghai Chang Zheng Hospital, Atlanta, GA, USA; 23Department of Hematology, Tufts Medical School, Boston, MA, USA; 24Department of Hematology Oncology, National University Cancer Institute, Singapore; 25Department of Hematology, University Hospital, Nantes, France; 26Department of Hematology, Erasmus MC, Rotterdam, The Netherlands; 27Department of Medicine, Center for Oncology, Hematology and Palliative Care, Wilhelminenspital, Vienna, Austria; 28Oschin Cancer Center, Los Angeles, CA, USA and 29Department of Clinical and Translational Medicine, University of Navarra, Pamplona, Spain. Correspondence: Dr EM Ocio, Department of Hematology, University Hospital and Cancer Research Center, University of Salamanca-IBSAL, IBMCC (USAL-CSIC), Paseo de San Vicente 58-182, 37007 Salamanca, Spain. E-mail: emocio@usal.es 30See Appendix. 31Current address: Levine Cancer Institute, Carolinas Healthcare System, Charlotte, NC, USA. Received 27 August 2013; revised 23 October 2013; accepted 7 November 2013; accepted article preview online 20 November 2013; advance online publication, 20 December 2013",
year = "2014",
month = mar,
doi = "10.1038/leu.2013.350",
language = "English (US)",
volume = "28",
pages = "525--542",
journal = "Leukemia",
issn = "0887-6924",
publisher = "Nature Publishing Group",
number = "3",
}