Two-, three- and four- drug regimens in the treatment of newly diagnosed patients with multiple myeloma including the effects of therapy with bortezomib

Abstract

The approval of bortezomib for the treatment of multiple myeloma in 2003 was a major breakthrough in the management of myeloma patients. Since then some combinations of bortezomib with other agents were proved to be active in preclinical investigations and were subsequently used in clinical trials testing new regimens. First observations with bortezomib-based combined therapies were made in patients with refractory and relapsed multiple myeloma, although there are rising data from studies with newly diagnosed myeloma patients, both elderly and autologous stem cell transplantation eligible. Commonly used combined therapies with bortezomib included regimens that combine this drug with corticosteroids, immunomodulatory drugs like thalidomide and lenalidomide, alkylating agents or anthracyclines. They were showed to be very active in producing high response rate and prolonged progression-free survival, although overall survival benefit was not demonstrated in a large proportion of studies, particularly in patients younger than 65 years and were given high-dose chemotherapy with autologous stem cell support. Moreover, multiagent combined therapies were showed to produce more adverse events and to be worse tolerated than combinations of bortezomib with only one or two drugs, which suggested a necessity for careful choosing a particular regimen to combine a good response rate and a survival benefit with a good quality of life, especially in elderly myeloma patients.

The last ASH conference 2012 provided further reports confirming the efficacy of bortezomib in the treatment of newly diagnosed myeloma, both in younger patients eligible for stem cell transplantation, and elderly who are not candidates for this procedure. Moreover, a few reports suggested that neurotoxicity associated with bortezomib might be significantly reduced with subcutaneous administration.