Bortezomib for previously untreated multiple myeloma.

INTRODUCTION: The paradigm of antimyeloma treatment has rapidly changed since the introduction of the first-in-class proteasome inhibitor bortezomib and the immunomodulatory drugs thalidomide and lenalidomide. AREAS COVERED: This manuscript discusses the most recent data on the frontline use of bortezomib and bortezomib-based combinations in multiple myeloma. Preclinical data, pharmacokinetics and pharmacodynamics of bortezomib are summarized, as well as published clinical trials of its use as a first-line treatment for transplant-eligible and elderly myeloma patients. Additionally, the use of bortezomib in particular myeloma subgroups, including patients with high-risk cytogenetics and renal insufficiency, is discussed. Finally, the prevention and management of bortezomib-induced side effects, including the latest data on weekly dosing for untreated elderly patients, is focused on. EXPERT OPINION: Bortezomib has become an important backbone of frontline myeloma treatment. Nevertheless, continued efforts to implement newer dosing regimens and to identify new partner drugs for bortezomib remain an important challenge.