New Strategies in the Treatment of Multiple Myeloma
+ Author Affiliations
- ↵*
Corresponding Author:
Nikhil C. Munshi, Medical Oncology/Hematologic Neoplasia, Dana-Farber, 450 Brookline Ave, Mayer 230, Boston, MA, 02215, United States Nikhil_Munshi@dfci.harvard.edu
Abstract
Multiple myeloma (MM) is the second most
common hematologic malignancy affecting terminally differentiated plasma
cells. Although
high-dose chemotherapy and autologous stem cell
transplantation improved survival in younger patients, the natural
history
of MM has been changed with the availability of
five new agents approved in last 10 years (thalidomide, bortezomib,
lenalidomide,
liposomal doxorubicin and carfilzomib). Despite
this significant improvement in overall outcome, MM remains incurable in
majority
of patients prompting continued search for
additional therapeutic options. Extensive molecular and genomic
characterization
of MM cells in its bone marrow milieu, which
affects myeloma cell growth and survival, has provided number of novel
drugable
targets and pathways. Perturbation of protein
catabolism at multiple levels has become an important target in MM.
Similarly
with improvements in monoclonal antibody generation
and vaccine development along with identification of number of cell
surface
and cellular targets have led to development of
various strategies including antibodies and antibody-drug conjugates
which
are under investigation both preclinically as well
as in early clinical studies. We propose that eventually,
molecularly-informed
multi-agent combination therapies will be required
to eliminate the MM cell clone for a long-term disease control.
- Received August 4, 2012.
- Revision received February 18, 2013.
- Accepted February 26, 2013.
- Copyright © 2013, American Association for Cancer Research.
