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 bortezomib. 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.
Bang
Soo-Mee
SM
Gachon Medical School, Incheon, Korea.
Lee
Jae Hoon
JH
Yoon
Sung-Soo
SS
Park
Seonyang
S
Min
Chang-Ki
CK
Kim
Chun-Choo
CC
Suh
Cheolwon
C
Sohn
Sang Kyun
SK
Min
Yoo-Hong
YH
Lee
Je-Jung
JJ
Kim
Kihyun
K
Seong
Chu-Myong
CM
Yoon
Hwi-Joong
HJ
Cho
Kyung Sam
KS
Jo
Deog-Yeon
DY
Lee
Kyung Hee
KH
Lee
Na-Ri
NR
Kim
Chul Soo
CS
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects*; D044466:Asian People; D001897:Boronic Acids / Q000008:administration & dosage / Q000009:adverse effects*; D000069286:Bortezomib; D003907:Dexamethasone / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D006801:Humans; D007723:Korea; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000150:complications / Q000401:mortality / Q000628:therapy*; D011719:Pyrazines / Q000008:administration & dosage / Q000009:adverse effects*; D012189:Retrospective Studies; D033581:Stem Cell Transplantation / Q000401:mortality; D013792:Thalidomide / Q000008:administration & dosage / Q000009:adverse effects; D014182:Transplantation, Autologous
D000970:Antineoplastic Agents; D001897:Boronic Acids; D011719:Pyrazines; D013792:Thalidomide; D000069286:Bortezomib; D003907:Dexamethasone