Bench-to-Bedside Translation of Targeted Therapies in Multiple Myeloma

Multiple myeloma (MM) is characterized by excess monoclonal plasma cells in the bone marrow (BM), in most cases associated with monoclonal protein in blood or urine. Nearly 50 years ago, the use of combined melphalan and prednisone was shown to extend median survival of patients with MM to 2-3 years. In an approach pioneered by Prof. Tim McElwain in the 1970s, high-dose melphalan followed by BM transplantation in the 1980s and peripheral blood stem cell rescue in the 1990s further increased median survival to 3-4 years. Since 1998, MM has represented a new paradigm in drug development due to the remarkable therapeutic efficacy of targeting tumor cells in their microenvironment^1,2—an approach perhaps best exemplified by the use of the proteasome inhibitor bortezomib and immunomodulatory drugs (IMiDs) thalidomide and lenalidomide to target the MM cell in the BM microenvironment. This approach has rapidly translated from bench to bedside, producing six new Food and Drug Administration (FDA)-approved treatments in the past 7 years and a doubling of patient survival from 3-4 to 7-8 years as a direct result.³ My colleagues and I have made contributions in the areas of identifying novel targets in the tumor and microenvironment, confirming the activity of inhibitors directed at these targets, and then leading clinical trials assessing the efficacy and safety of these agents...

*For a PDF of the full article, click on the link to the left of this introduction.

Multiple myeloma (MM) is characterized by excess monoclonal plasma cells in the bone marrow (BM), in most cases associated with monoclonal protein in blood or urine. Nearly 50 years ago, the use of combined melphalan and prednisone was shown to extend median survival of patients with MM to 2-3 years. In an approach pioneered by Prof. Tim McElwain in the 1970s, high-dose melphalan followed by BM transplantation in the 1980s and peripheral blood stem cell rescue in the 1990s further increased median survival to 3-4 years. Since 1998, MM has represented a new paradigm in drug development due to the remarkable therapeutic efficacy of targeting tumor cells in their microenvironment^1,2—an approach perhaps best exemplified by the use of the proteasome inhibitor bortezomib and immunomodulatory drugs (IMiDs) thalidomide and lenalidomide to target the MM cell in the BM microenvironment. This approach has rapidly translated from bench to bedside, producing six new Food and Drug Administration (FDA)-approved treatments in the past 7 years and a doubling of patient survival from 3-4 to 7-8 years as a direct result.³ My colleagues and I have made contributions in the areas of identifying novel targets in the tumor and microenvironment, confirming the activity of inhibitors directed at these targets, and then leading clinical trials assessing the efficacy and safety of these agents...

*For a PDF of the full article, click on the link to the left of this introduction.

Multiple myeloma (MM) is characterized by excess monoclonal plasma cells in the bone marrow (BM), in most cases associated with monoclonal protein in blood or urine. Nearly 50 years ago, the use of combined melphalan and prednisone was shown to extend median survival of patients with MM to 2-3 years. In an approach pioneered by Prof. Tim McElwain in the 1970s, high-dose melphalan followed by BM transplantation in the 1980s and peripheral blood stem cell rescue in the 1990s further increased median survival to 3-4 years. Since 1998, MM has represented a new paradigm in drug development due to the remarkable therapeutic efficacy of targeting tumor cells in their microenvironment^1,2—an approach perhaps best exemplified by the use of the proteasome inhibitor bortezomib and immunomodulatory drugs (IMiDs) thalidomide and lenalidomide to target the MM cell in the BM microenvironment. This approach has rapidly translated from bench to bedside, producing six new Food and Drug Administration (FDA)-approved treatments in the past 7 years and a doubling of patient survival from 3-4 to 7-8 years as a direct result.³ My colleagues and I have made contributions in the areas of identifying novel targets in the tumor and microenvironment, confirming the activity of inhibitors directed at these targets, and then leading clinical trials assessing the efficacy and safety of these agents...

*For a PDF of the full article, click on the link to the left of this introduction.