Targeted Therapy of Multiple Myeloma: The Changing Paradigm at the Beginning of the New Millennium
Anna Grazia Recchia,
Multiple myeloma (MM) is a malignant hematological neoplasmand constitutes 10% of blood cancers.
Recently, it has become evident that almost all cases of MM are preceded by gammopathy of undetermined significance
(MGUS). MM is diagnosed by the presence of paraprotein in serum or urine, detected by serum electrophoresis and
immunofixation, infiltration of malignant plasma cells in the bone marrow and related organ, or tissue damage.
Cytogenetic status, International Staging System (ISS) and the quality of response to therapy are the most important
prognostic factors. In the last decade the availability of new effective drugs, such as thalidomide, lenalidomide and
bortezomib have provided a new therapeutic scenario expected to impact favorably on the outcome of MM patients.
Today, for younger patients a triple-agent induction regimen incorporating novel agents followed by autologous stem cell
transplantation (ASCT) is the best approach. In this setting ongoing clinical trials are evaluating the efficacy of
consolidation and maintenance therapy based on the use of new drugs. For patients noteligible for ASCT the best initial
regimens are combination therapy with melphalan and prednisone plus either thalidomide or bortezomibor the
combination of lenalidomide and dexamethasone. Supportive therapy includes the use of erythropoietin and
bisphosphonates according to the updated guidelines. In the future the identification of candidate therapeutic targets
through gene expression profiling (GEP) and single-nucleotide polymorphism (SNP) analysis, as well as the availability
of the targeted investigative agents will lead to a substantial progress in the development and implementation of
personalized medicine in MM.
Keywords: Bortezomib, lenalidomide, multiple myeloma, stem cell transplantation, thalidomide, therapy, Allogeneic transplantation with reducedintensity conditioning, Autologous stem cell transplantation, Beta2-microglobulin, Conventional cytogenetics, International Staging System, Receptor activator of nuclear factorkappa B ligand, Very good partial remission, Positron emission tomography, Monoclonal gammopathy of undetermined significance.
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