Proteasome inhibitors in multiple myeloma: 10 years later.
Proteasome inhibition has emerged as an important therapeutic strategy in multiple myeloma (MM). Since the publication of the first phase 1 trials of bortezomib 10 years ago, this first-in-class proteasome inhibitor (PI) has contributed substantially to the observed improvement in survival in MM patients over the past decade. Although first approved as a single agent in the relapsed setting, bortezomib is now predominantly used in combination regimens. Furthermore, the standard twice-weekly schedule may be replaced by weekly infusion, especially when bortezomib is used as part of combination regimens in frontline therapy. Indeed, bortezomib is an established component of induction therapy for patients eligible or ineligible for autologous stem cell transplantation. Bortezomib has also been incorporated into conditioning regimens before autologous stem cell transplantation, as well as into post-ASCT consolidation therapy, and in the maintenance setting. In addition, a new route of bortezomib administration, subcutaneous infusion, has recently been approved. Recently, several new agents have been introduced into the clinic, including carfilzomib, marizomib, and MLN9708, and trials investigating these "second-generation" PIs in patients with relapsed/refractory MMs have demonstrated positive results. This review provides an overview of the role of PIs in the treatment of MM, focusing on developments over the past decade.
Hematology Department, University Hospital Hotel-Dieu, Nantes, France. philippe.moreau@chu-nantes.fr
Philippe
P
Moreau
Paul G
PG
Richardson
Michele
M
Cavo
Robert Z
RZ
Orlowski
Jesús F
JF
San Miguel
Antonio
A
Palumbo
Jean-Luc
JL
Harousseau
D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D001897:Boronic Acids / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D000069286:Bortezomib; D015853:Cysteine Proteinase Inhibitors / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D008495:Medical Oncology / Q000379:methods / Q000639:trends*; D009101:Multiple Myeloma / Q000188:drug therapy*; D061988:Proteasome Inhibitors; D011719:Pyrazines / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D013997:Time Factors
D000970:Antineoplastic Agents; D001897:Boronic Acids; D015853:Cysteine Proteinase Inhibitors; D061988:Proteasome Inhibitors; D011719:Pyrazines; D000069286:Bortezomib