Bortezomib is a first-in-class proteasome inhibitor that has shown remarkable efficacy in multiple myeloma. Bortezomib specifically targets the ubiquitin-proteasome pathway; the proteasome plays a key role in the degradation of ubiquinated proteins in general, and specifically proteins that control tumor cell growth and survival. By targeting the proteasome and acting on the multiple myeloma cells as well as the microenvironment, bortezomib has been shown to increase response in patients with multiple myeloma, especially in patients with relapsed and refractory disease. Bortezomib is currently indicated for the treatment of multiple myeloma, including use as first line or in second-line treatment after first relapse.Bortezomib can be combined with other agents and much investigation is going on.
For amyloidosis, several studies show that bortezomib is a active drug with high response rates in various lines of therapy. These include 1 phase II clinical study (Kastritis et al, 2007), small case series (Wechalekar et al, 2008), and case reports (Borde et al, 2008). Data showing hematologic overall response rate exceeding 66 percent and complete response rates of up to 37 percent seen with single agent VELCADE were presented at the Annual Meeting of the American Society of Clinical Oncology (ASCO) held in Chicago, Illinois, June 4-8, 2010.
NCCN’s Drug and Biologics Compendium lists systemic light chain amyloidosis as an indication for bortzomib as do NCCN guidelines (2011).
Carlson, Robert H. Amyloidosis: High Hematologic Response Rates with Bortezomib, Oncology Times: 10 August 2010 – Volume 32 – Issue 15 – pp 16-17
Mario Dicatoa et al, Management of Multiple Myeloma with Bortezomib: Experts Review the Data and Debate the Issues Oncology Vol. 70, No. 6, 2006
Sitia R, Palladini G, Merlini G. Bortezomib in the treatment of AL amyloidosis: Targeted therapy? Haematologica. 1007;92(10):1302-1305.
National Comprehensive Cancer Network (NCCN). Bortezomib. In: NCCN Drugs & Biologics Compendium. Fort Washington, PA: NCCN; 2008.
National Comprehensive Cancer Network (NCCN). Multiple myeloma. NCCN Clinical Practice Guidelines in Oncology v.2.2009. Fort Washington, PA: NCCN; 2009.
Comenzo RL. Managing systemic light-chain amyloidosis. J Natl Compr Canc Netw. 2007;5(2):179-187.
Kastritis E, Anagnostopoulos A, Roussou M, et al. Treatment of light chain (AL) amyloidosis with the combination of bortezomib and dexamethasone. Haematologica. 2007;92(10):1351-1358.
Wechalekar AD, Lachmann HJ, Offer M, et al. Efficacy of bortezomib in systemic AL amyloidosis with relapsed/refractory clonal disease. Haematologica. 2008;93(2):295-298.