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Reviews

Targeted therapeutics for multiple myeloma: The arrival of a risk-stratified approach

Division of Hematology-Oncology, Mayo Clinic, Scottsdale, Arizona

Requests for reprints: Rafael Fonseca, Mayo Clinic, 13208 East Shea Boulevard, Collaborative Research Building, 3-006, Scottsdale, AZ 85259-5494. Phone: 480-301-6118; Fax: 480-301-8387. E-mail: fonseca.rafael{at}mayo.edu

Multiple myeloma (MM) remains an incurable hematologic malignancy characterized by frequent early responses, inevitably followed by treatment relapse. Until recently, few effective therapies existed. Indeed, the use of alkylating agents and corticosteroids had remained the treatment of choice for almost four decades. Several novel agents for MM have now become available, including the immunomodulatory drugs thalidomide and lenalidomide, as well as the proteasome inhibitor bortezomib. Each of these agents is undergoing extensive clinical evaluation in combination with other therapies to produce unprecedented response rates in newly diagnosed and relapsed MM. Nevertheless, relapse remains universal and further therapeutics with broad activity are required. Importantly, it has become clear that pivotal genetic events are the primary harbingers of clinical outcome and novel targeted therapy approaches using existing approved drugs or novel agents, which address that disrupted signaling pathways are now in various stages of clinical testing. It seems increasingly likely that novel drug combinations, which together turn off these critical Achilles heels, will become the standard of care and that treatment will become increasingly personalized and guided by genetic testing and prognostic factors. [Mol Cancer Ther 2007;6(3):802–10]

¹ P.L. Bergsagel and R. Fonseca, personal communication, September 2006.

² http://www.swog.org/Visitors/ViewProtocolDetails.asp?ProtocolID=1963

³ S. Treon, personal communication. American Society of Hematology 2005.

⁴ B. Barlogie, personal communication, June 2006.

⁵ A. Keith Stewart, personal communication.

Received 10/ 9/06; revised 1/ 3/07; accepted 1/30/07.

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