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

Ocio, E. M.; Richardson, P. G.; Rajkumar, S. V.; Palumbo, A.; Mateos, M. V.; Orlowski, R.; Kumar, S.; Usmani, S.; Roodman, D. and Niesvizky, R., et al. (2014) In Leukemia 28(3). p.525-542
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... (More)
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. (Less)
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publication status
published
subject
keywords
multiple myeloma, new drugs, targeted agents, phase I clinical trials
in
Leukemia
volume
28
issue
3
pages
525 - 542
publisher
Nature Publishing Group
external identifiers
  • wos:000332845700006
  • scopus:84895784261
ISSN
1476-5551
DOI
10.1038/leu.2013.350
language
English
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yes
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f39311ce-4b00-47c6-ba90-c08c64ac269e (old id 4410652)
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2014-05-05 07:19:14
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2017-11-05 04:11:04
@article{f39311ce-4b00-47c6-ba90-c08c64ac269e,
  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.},
  author       = {Ocio, E. M. and Richardson, P. G. and Rajkumar, S. V. and Palumbo, A. and Mateos, M. V. and Orlowski, R. and Kumar, S. and Usmani, S. and Roodman, D. and Niesvizky, R. and Einsele, H. and Anderson, K. C. and Dimopoulos, M. A. and Avet-Loiseau, H. and Mellqvist, U-H and Turesson, Ingemar and Merlini, G. and Schots, R. and McCarthy, P. and Bergsagel, L. and Chim, C. S. and Lahuerta, J. J. and Shah, J. and Reiman, A. and Mikhael, J. and Zweegman, S. and Lonial, S. and Comenzo, R. and Chng, W. J. and Moreau, P. and Sonneveld, P. and Ludwig, H. and Durie, B. G. M. and Miguel, J. F. S.},
  issn         = {1476-5551},
  keyword      = {multiple myeloma,new drugs,targeted agents,phase I clinical trials},
  language     = {eng},
  number       = {3},
  pages        = {525--542},
  publisher    = {Nature Publishing Group},
  series       = {Leukemia},
  title        = {New drugs and novel mechanisms of action in multiple myeloma in 2013: a report from the International Myeloma Working Group (IMWG)},
  url          = {http://dx.doi.org/10.1038/leu.2013.350},
  volume       = {28},
  year         = {2014},
}