Emerging therapies for multiple myeloma

Abstract

Multiple myeloma (MM) is a clonal plasma cell malignancy clinically characterized by osteolytic lesions, immunodeficiency, and renal disease. There are an estimated 750,000 people diagnosed with MM worldwide, with a median overall survival of 3 – 5 years. Besides chromosomal aberrations, translocations, and mutations in essential growth and tumor-suppressor genes, accumulating data strongly highlight the pathophysiologic role of the bone marrow (BM) microenvironment in MM pathogenesis. Based on this knowledge, several novel agents have been identified, and treatment options in MM have fundamentally changed during the last decade. Thalidomide, bortezomib, and lenalidomide have been incorporated into conventional cytotoxic and transplantation regimens, first in relapsed and refractory and now also in newly diagnosed MM. Despite these significant advances, there remains an urgent need for more efficacious and tolerable drugs. Indeed, a plethora of preclinical agents awaits translation from the bench to the bedside. This article reviews the scientific rationale of new therapy regimens and newly identified therapeutic agents – small molecules as well as therapeutic antibodies – that hold promise to further improve outcome in MM.

Keywords::

• bone marrow microenvironment
• combination therapy
• multiple myeloma

Acknowledgements

This work was supported by the Multiple Myeloma Research Foundation (IMF) Senior Research Grant Award and Dunkin' Donuts Rising Star Award (KP), International Myeloma Foundation (MMRF) Junior Research Grant Award (SV) as well as National Institutes of Health Grants IP50 CA100707, PO-1 78378, and RO-1 CA 50947; The Myeloma Research Fund; and the LeBow Family Fund to Cure Myeloma (KCA).