TY - JOUR
T1 - Novel approaches to treatment of double-refractory multiple myeloma
AU - Lee, Hans C.
AU - Shah, Jatin J.
AU - Orlowski, Robert Z.
PY - 2013
Y1 - 2013
N2 - Multiple myeloma (MM) refractory to both proteasome inhibitors and immunomodulatory agents (IMiDs; double-refractory myeloma) has a poor prognosis. With the more frequent use of these agents as part of initial therapy, and then in the maintenance setting until disease progression, such drug resistance is an emerging problem of great significance. New therapeutic strategies are clearly needed for this patient population, including the development of more potent agents within existing antimyeloma drug classes, exploration of rational combinations of both novel and conventional drugs, and validation of new myeloma drug targets. Several approaches have shown substantial promise, including use of the second-generation proteasome inhibitor carfilzomib and the third-generation IMiD pomalidomide, which led to the recent regulatory approval of both agents. In addition, the kinesin-spindle protein KSP inhibitor ARRY-520 has shown activity as a first-in-class drug in myeloma therapeutics, whereas the histone deacetylase (HDAC) inhibitors vorinostat and panobinostat have demonstrated efficacy when used in rational combinations. This overview provides a summary of novel agents that have shown activity in double-refractory myeloma in recent phase II and III clinical trials, and a framework for future studies that will help to improve outcomes in this patient population.
AB - Multiple myeloma (MM) refractory to both proteasome inhibitors and immunomodulatory agents (IMiDs; double-refractory myeloma) has a poor prognosis. With the more frequent use of these agents as part of initial therapy, and then in the maintenance setting until disease progression, such drug resistance is an emerging problem of great significance. New therapeutic strategies are clearly needed for this patient population, including the development of more potent agents within existing antimyeloma drug classes, exploration of rational combinations of both novel and conventional drugs, and validation of new myeloma drug targets. Several approaches have shown substantial promise, including use of the second-generation proteasome inhibitor carfilzomib and the third-generation IMiD pomalidomide, which led to the recent regulatory approval of both agents. In addition, the kinesin-spindle protein KSP inhibitor ARRY-520 has shown activity as a first-in-class drug in myeloma therapeutics, whereas the histone deacetylase (HDAC) inhibitors vorinostat and panobinostat have demonstrated efficacy when used in rational combinations. This overview provides a summary of novel agents that have shown activity in double-refractory myeloma in recent phase II and III clinical trials, and a framework for future studies that will help to improve outcomes in this patient population.
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U2 - 10.1200/EdBook_AM.2013.33.e302
DO - 10.1200/EdBook_AM.2013.33.e302
M3 - Review article
C2 - 23714530
AN - SCOPUS:84946220659
SN - 1548-8756
JO - American Society of Clinical Oncology educational book / ASCO. American Society of Clinical Oncology. Meeting
JF - American Society of Clinical Oncology educational book / ASCO. American Society of Clinical Oncology. Meeting
ER -