Format

Send to

Choose Destination
Leukemia. 2014 Mar;28(3):525-42. doi: 10.1038/leu.2013.350. Epub 2013 Nov 20.

New drugs and novel mechanisms of action in multiple myeloma in 2013: a report from the International Myeloma Working Group (IMWG).

Author information

1
Department of Hematology, University Hospital and Cancer Research Center, University of Salamanca-IBSAL, IBMCC (USAL-CSIC), Salamanca, Spain.
2
Department of Medicine, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
3
Department of Hematology, Mayo Clinic, Rochester, MN, USA.
4
Department of Hematology, University of Torino, Torino, Italy.
5
Department of Lymphoma/Myeloma, MD Anderson Cancer Center, Houston, TX, USA.
6
M.I.R.T. UAMS, Little Rock, AR, USA.
7
Director of Hematology/Oncology, Indiana University, Indianapolis, IN, USA.
8
Department of Hematology, Weill Cornell Medical College, New York, NY, USA.
9
Department of Internal Medicine, University of Wurzburg, Wurzburg, Germany.
10
School of Medicine, University of Athens, Athens, Greece.
11
Department of Hematology, University of Toulouse, Toulouse, France.
12
Department of Medicine, Section of Hematology, Sahlgrenska University Hospital, Gothenburg, Sweden.
13
Department of Medicine, Section of Hematology, Skane University Hospital, Malmo, Sweden.
14
Department of Molecular Medicine, Univeristy of Pavia, Pavia, Italy.
15
Department of Clinical Hematology and Stem Cell Laboratory, University Ziekenhuis, Brussels, Belgium.
16
Department of Medicine, Roswell Park Cancer Institute, Buffalo, NY, USA.
17
Division of Hematology and Oncology, Mayo Clinic, Scottsdale, AZ, USA.
18
Department of Hematology, Queen Mary Hospital, Hong Kong.
19
Department of Hematology, Hospital Universitario 12 de Octubre, Madrid, Spain.
20
Department of Oncology, University of New Brunswick, Saint John Regional Hospital, St John, NB, Canada.
21
Department of Hematology, VU University Medical Center, Amsterdam, The Netherlands.
22
Department of Hematology and Medical Oncology, Shanghai Chang Zheng Hospital, Atlanta, GA, USA.
23
Department of Hematology, Tufts Medical School, Boston, MA, USA.
24
Department of Hematology Oncology, National University Cancer Institute, Singapore.
25
Department of Hematology, University Hospital, Nantes, France.
26
Department of Hematology, Erasmus MC, Rotterdam, The Netherlands.
27
Department of Medicine, Center for Oncology, Hematology and Palliative Care, Wilhelminenspital, Vienna, Austria.
28
Oschin Cancer Center, Los Angeles, CA, USA.
29
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.

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.

PMID:
24253022
PMCID:
PMC4143389
DOI:
10.1038/leu.2013.350
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center