Person:

Roccaro, Aldo M.

Melphalan combined with prednisone (MP) has long been the historical treatment of reference for a large proportion of elderly myeloma (MM) patients ineligible for autologous stem cell transplantation, and is still the backbone of new regimens that include the new era of novel agents. Melphalan–prednisone–thalidomide (MPT) and melphalan–prednisone–bortezomib (Velcade®, MPV), proved superior to MP, currently appear to be the treatments of choice for this population. In the near future melphalan–prednisone–lenalidomide (Revlimid®, MPR) will also provide a third therapeutic option (MPT, MPV, and MPR), in elderly multiple myeloma, eventually. These options could lead to more personalized treatment approaches, based on patient comorbidities, as the three novel agents have somewhat different toxicity profiles. Dexamethasone-based regimen is another option and questions regarding the relative efficacy of melphalan-based versus low-dose dexamethasone-based regimens will require randomized phase III trials. More intensive approaches with new drug combinations or with the incorporation of polyethylene glycolated (PEGylated) liposomal doxorubicin will also require additional studies. Additionally, the important issue of maintenance treatment needs to be further investigated. These new and emerging therapies offer multiple effective treatment options for MM patients and greatly enhanced treatment strategies for clinicians.

The paradigm for the treatment of monoclonal gammopaties has dramatically changed: therapeutic options in multiple myeloma (MM) have evolved from the introduction of melphalan and prednisone in the 1960s, high-dose chemotherapy and stem cell transplantation in the late 1980s and 1990s, to the rapid introduction of small novel molecules within the last seven years. Based on the understanding of the complex interaction of the MM cells with the bone marrow microenvironment and the signaling pathways that are dysregulated in this process, a number of novel therapeutic agents are now available. Specifically, three novel agents with a specific-targeted anti-MM activity, have been FDA-approved for the treatment of this disease, namely Bortezomib, thalidomide, and lenalidomide which are now all playing a key role in the treatment of MM. The success of targeted therapy in MM has since led to the development and investigation of more than 30 new compounds in this disease and in other plasma cell dyscrasias such as Waldenström’s macroglobulinemia and primary amyloidosis, both in the preclinical settings and as part of clinical trials.