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.
authors.affiliation: Department of Hematology, University Hospital and Cancer Research Center, University of Salamanca-IBSAL, IBMCC (USAL-CSIC), Salamanca, Spain.
authors.forename: E M
authors.initials: EM
authors.lastname: Ocio
authors.affiliation: Department of Medicine, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
authors.forename: P G
authors.initials: PG
authors.lastname: Richardson
authors.affiliation: Department of Hematology, Mayo Clinic, Rochester, MN, USA.
authors.forename: S V
authors.initials: SV
authors.lastname: Rajkumar
authors.affiliation: Department of Hematology, University of Torino, Torino, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Palumbo
authors.affiliation: Department of Hematology, University Hospital and Cancer Research Center, University of Salamanca-IBSAL, IBMCC (USAL-CSIC), Salamanca, Spain.
authors.forename: M V
authors.initials: MV
authors.lastname: Mateos
authors.affiliation: Department of Lymphoma/Myeloma, MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: R
authors.initials: R
authors.lastname: Orlowski
authors.affiliation: Department of Hematology, Mayo Clinic, Rochester, MN, USA.
authors.forename: S
authors.initials: S
authors.lastname: Kumar
authors.affiliation: M.I.R.T. UAMS, Little Rock, AR, USA.
authors.forename: S
authors.initials: S
authors.lastname: Usmani
authors.affiliation: Director of Hematology/Oncology, Indiana University, Indianapolis, IN, USA.
authors.forename: D
authors.initials: D
authors.lastname: Roodman
authors.affiliation: Department of Hematology, Weill Cornell Medical College, New York, NY, USA.
authors.forename: R
authors.initials: R
authors.lastname: Niesvizky
authors.affiliation: Department of Internal Medicine, University of Wurzburg, Wurzburg, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Einsele
authors.affiliation: Department of Medicine, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
authors.forename: K C
authors.initials: KC
authors.lastname: Anderson
authors.affiliation: School of Medicine, University of Athens, Athens, Greece.
authors.forename: M A
authors.initials: MA
authors.lastname: Dimopoulos
authors.affiliation: Department of Hematology, University of Toulouse, Toulouse, France.
authors.forename: H
authors.initials: H
authors.lastname: Avet-Loiseau
authors.affiliation: Department of Medicine, Section of Hematology, Sahlgrenska University Hospital, Gothenburg, Sweden.
authors.forename: U-H
authors.initials: UH
authors.lastname: Mellqvist
authors.affiliation: Department of Medicine, Section of Hematology, Skane University Hospital, Malmo, Sweden.
authors.forename: I
authors.initials: I
authors.lastname: Turesson
authors.affiliation: Department of Molecular Medicine, Univeristy of Pavia, Pavia, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Merlini
authors.affiliation: Department of Clinical Hematology and Stem Cell Laboratory, University Ziekenhuis, Brussels, Belgium.
authors.forename: R
authors.initials: R
authors.lastname: Schots
authors.affiliation: Department of Medicine, Roswell Park Cancer Institute, Buffalo, NY, USA.
authors.forename: P
authors.initials: P
authors.lastname: McCarthy
authors.affiliation: Division of Hematology and Oncology, Mayo Clinic, Scottsdale, AZ, USA.
authors.forename: L
authors.initials: L
authors.lastname: Bergsagel
authors.affiliation: Department of Hematology, Queen Mary Hospital, Hong Kong.
authors.forename: C S
authors.initials: CS
authors.lastname: Chim
authors.affiliation: Department of Hematology, Hospital Universitario 12 de Octubre, Madrid, Spain.
authors.forename: J J
authors.initials: JJ
authors.lastname: Lahuerta
authors.affiliation: Department of Lymphoma/Myeloma, MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: J
authors.initials: J
authors.lastname: Shah
authors.affiliation: Department of Oncology, University of New Brunswick, Saint John Regional Hospital, St John, NB, Canada.
authors.forename: A
authors.initials: A
authors.lastname: Reiman
authors.affiliation: Division of Hematology and Oncology, Mayo Clinic, Scottsdale, AZ, USA.
authors.forename: J
authors.initials: J
authors.lastname: Mikhael
authors.affiliation: Department of Hematology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: S
authors.initials: S
authors.lastname: Zweegman
authors.affiliation: Department of Hematology and Medical Oncology, Shanghai Chang Zheng Hospital, Atlanta, GA, USA.
authors.forename: S
authors.initials: S
authors.lastname: Lonial
authors.affiliation: Department of Hematology, Tufts Medical School, Boston, MA, USA.
authors.forename: R
authors.initials: R
authors.lastname: Comenzo
authors.affiliation: Department of Hematology Oncology, National University Cancer Institute, Singapore.
authors.forename: W J
authors.initials: WJ
authors.lastname: Chng
authors.affiliation: Department of Hematology, University Hospital, Nantes, France.
authors.forename: P
authors.initials: P
authors.lastname: Moreau
authors.affiliation: Department of Hematology, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: P
authors.initials: P
authors.lastname: Sonneveld
authors.affiliation: Department of Medicine, Center for Oncology, Hematology and Palliative Care, Wilhelminenspital, Vienna, Austria.
authors.forename: H
authors.initials: H
authors.lastname: Ludwig
authors.affiliation: Oschin Cancer Center, Los Angeles, CA, USA.
authors.forename: B G M
authors.initials: BG
authors.lastname: Durie
authors.affiliation: 1] Department of Hematology, University Hospital and Cancer Research Center, University of Salamanca-IBSAL, IBMCC (USAL-CSIC), Salamanca, Spain [2] Department of Clinical and Translational Medicine, University of Navarra, Pamplona, Spain.
authors.forename: J F S
authors.initials: JF
authors.lastname: Miguel
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D006801:Humans; D009101:Multiple Myeloma / Q000188:drug therapy*
chemical_list: D000970:Antineoplastic Agents