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 Printable version |
Innovations in the treatment of multiple myeloma |
Hématologie. Volume 10, Number 4, 287-95, Juillet-août 2004, Revue
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 Résumé
Article gratuit
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Author(s) : Xavier Leleu Frédérique Kuhnovski Valérie Coiteux Louis Terriou Thierry Facon |
Summary : Multiple myeloma (MM) comprises about 1 per cent of all malignant disease and 10‐12% of haematological malignancies. In most hospital series, the median age is 65 years. Autologous stem cell transplantation (ASCT) has been widely used in MM in the past 15 years. Several important issues have been clarified \; low toxic death rate (1‐3%), superiority of ASCT compared to conventional chemotherapy, source of stem cells, conditioning regimen. Other issues are still being debated like the role of tandem transplantation and maintenance therapy after ASCT. The results of non myeloablative allogeneic transplantation are also under evaluation. Potent bisphosphonates for treatment of MM bone disease and human recombinant erythropoietin for anaemia are frequently part of the therapeutic programs. Novel biologically‐based therapies target the MM cell as well as its bone marrow (BM) microenvironment. Increased BM antiogenesis has provided the empiric rationale for the use of thalidomide which has achieved a 30‐50% response rate in refractory MM. The thalidomide analogue IMiD‐3 (Revimid
®, formerly CC‐5013) has achieved promising results in phase I and II studies, even in patients refractory to thalidomide (30% partial response rate). There is now evidence that the thalidomide and IMiDs act not only to inhibit angiogenesis but also to directly induce apoptosis in MM cells, abrogate the adhesion of MM cells to BM stromal cells and block the increased secretion of MM growth, survival and migratory factors. The proteasome inhibitor, bortezomib, has also demonstrated clinical promise in refractory MM. The recently completed phase II study found a decrease of 90% or greater in MM paraprotein in 13% of patients and at least a partial response in 32% of patients. Numerous other strategies or molecules are currently under evaluation, like immune therapy (vaccination with idiotype, DNA, tumor‐associated antigens, immunotherapy with idiotype pulsed dendritic cells), arsenic trioxyde, blockade of the IGF‐1\\IGF‐1R system, histone deacetylase and Hsp90 inhibitors, and the Bcl‐2 antisense strategy. |
Keywords : multiple myeloma, autologous ASCT, thalidomide |
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