A Multicenter Retrospective Analysis of Adverse Events in Korean Patients Using Bortezomib for Multiple Myeloma
The proteasome inhibitor bortezomib has demonstrated clinical activity in patients with multiple myeloma (MM). Adverse events, including thrombocytopenia and peripheral neuropathy, have affected 30% to 60% of patients overall, and interrupted therapy in 10% to 20%. No prior toxicity data are available for Asian patients who have used bortezomib for MM. We used National Cancer Institute Common Terminology Criteria for Adverse Events, version 3.0, to review the clinical records of patients with an MM diagnosis from 25 centers in Korea. The included patients were treated with bortezomib alone or in combination with other agents, including thalidomide. Ninety-five MM patients were treated. The patients had a median age of 60 years (range, 42-77 years). The median number of previous treatments was 3 (range, 0–10), and 39% of the patients had been treated with 4 or more major classes of agents, including thalidomide (67%), and autologous stem cell transplantation (51%). Regimens included bortezomib only in 38 patients (40%), bortezomib plus dexamethasone in 34 patients (36%), and bortezomib plus a thalidomide-containing regimen in 23 patients (24%). The analysis of patient response to therapy revealed a complete response (CR) or a near-CR in 31 patients (33%) and a partial response in 30 patients (32%), for an objective response rate of 65% in 93 patients. The most common adverse events reported were thrombocytopenia (47%), sensory neuropathy (42%), anemia (31%), and leukopenia (31%). Thirteen patients (14%) stopped therapy because of adverse events (neuropathy, 8; infection, 4; diarrhea, 1). Neuropathy greater than grade 2 was more frequent in patients who received 4 or more prior therapy regimens (17/37) than in those who received 3 or fewer (14/58). In addition, therapy including thalidomide was significantly correlated with neuropathy of grades 1 to 3 (P = .001). We identified 6 therapy-related deaths (6%) within 20 days after the last dose of borte-zomib. The causes of death were infection in 3 patients, disease progression in 2 patients, and suicide in 1 patient. The incidences of thrombocytopenia and neurotoxicity were similar; however, gastrointestinal toxicities were relatively low in Korean patients compared with those reported in Western studies. Significant neuropathy was associated with the number of prior regimens and combination with thalidomide. These findings provide useful information for clinicians and patients using bortezomib.
Key wordsBortezomib Adverse events Neurotoxicity Thalidomide Multiple myeloma
Unable to display preview. Download preview PDF.
- 1.SH Yang, TY Kim, BK Kim, et al. A statistical study of multiple myeloma in Korea [in Korean]. Korean J Hematol. 1995;30:345–361.Google Scholar
- 2.Ministry of Health and Welfare, Republic of Korea. Annual Report of Korean Cancer (2002.1—2002.12); 2004. Available at: http://www.ncc.re.kr.Google Scholar
- 10.Alexanian R, Wang LM, Weber DM, et al. VTD (Velcade, thalido-mide, dexamethasone) as primary therapy for newly-diagnosed multiple myeloma [abstract]. Blood. 2004;100(suppl 1):64a.Google Scholar
- 12.Blade J, Samson D, Reece D, et al, on behalf of the Myeloma Subcommittee of the EBMT (European Group for Blood and Marrow Transplantation), Chronic Leukaemia Working Party and the Myeloma Working committee of the IBMTR (International Bone Marrow Transplant Registry), and ABMTR (Autologous Blood and Marrow Transplant Registry). Criteria for evaluating disease response and progression in patients with multiple myeloma treated by high-dose therapy and haemopoietic stem cell transplantation. Br J Haematol. 1998;102:1115–1123.CrossRefGoogle Scholar
- 13.Cancer Therapy Evaluation Program. Common Terminology Criteria for Adverse Events v3.0 (CTCAE). 2003. Available at: http://ctep.cancer.gov/reporting/ctcnew.html. Accessed March 23, 2006.Google Scholar
- 16.Richardson P, Briemberg H, Jagannath S, et al. Characterization and reversibility of peripheral neuropathy in patients with advanced multiple myeloma treated with bortezomib (Velcade®): the SUMMIT and CREST study group. In: Programs and Abstracts of the 9th Annual Congress of the European Hematology Association; June 11–13, 2004; Geneva, Switzerland. Abstract 368a.Google Scholar