Proteasome inhibitors in multiple myeloma: 10 years later

• Published in: Blood Vol. 120; no. 5; pp. 947 - 959
• Main Authors: Moreau, Philippe, Richardson, Paul G., Cavo, Michele, Orlowski, Robert Z., San Miguel, Jesús F., Palumbo, Antonio, Harousseau, Jean-Luc
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 02.08.2012; Americain Society of Hematology; American Society of Hematology
• Subjects: Animals; Antineoplastic Agents - adverse effects; Antineoplastic Agents - pharmacology; Antineoplastic Agents - therapeutic use; Biological and medical sciences; Boronic Acids - adverse effects; Boronic Acids - pharmacology; Boronic Acids - therapeutic use; Bortezomib; Cysteine Proteinase Inhibitors - adverse effects; Cysteine Proteinase Inhibitors - pharmacology; Cysteine Proteinase Inhibitors - therapeutic use; Hematologic and hematopoietic diseases; Humans; Immunodeficiencies. Immunoglobulinopathies; Immunoglobulinopathies; Immunopathology; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Medical Oncology - methods; Medical Oncology - trends; Medical sciences; Multiple Myeloma - drug therapy; Proteasome Inhibitors; Pyrazines - adverse effects; Pyrazines - pharmacology; Pyrazines - therapeutic use; Review; Time Factors; Immunopathology; Immunoglobulinopathy; Hematology; Lymphoproliferative syndrome; Proteasome inhibitor; Malignant hemopathy; Myeloma; Cancer
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2012-04-403733

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.