Safety and efficacy of bortezomib in high-risk and elderly patients with relapsed multiple myeloma.
Adverse prognostic factors in multiple myeloma include advanced age, number of prior therapies, and higher International Staging System (ISS) disease stage. In the international, randomised, phase-3 Assessment of Proteasome Inhibition for Extending Remissions (APEX) study, bortezomib demonstrated significantly longer time to progression (TTP), higher response rates and improved survival compared with high-dose dexamethasone in patients with relapsed multiple myeloma following one to three prior therapies. In this APEX subgroup analysis, efficacy of bortezomib and dexamethasone was compared in elderly (age > or =65 years) and high-risk (>1 prior line of therapy; ISS stage II/III; refractory to prior therapy) patients. Bortezomib demonstrated substantial clinical activity in these patients. Response rate (34-40% vs. 13-19%), including complete response rate (5-8% vs. 0-1%), was significantly higher with bortezomib versus dexamethasone in all four subgroups. Similarly, median TTP was significantly longer with bortezomib versus dexamethasone, and 1-year survival probability was significantly higher in all subgroups. As in the total APEX population, rates of grade 3/4 adverse events were higher in bortezomib- versus dexamethasone-treated patients aged > or =65 years and with >1 prior line, while rates of serious adverse events were similar; toxicities generally proved manageable. Bortezomib should be considered an appropriate treatment for elderly and high-risk patients with relapsed multiple myeloma.
Richardson
Paul G
PG
Medical Oncology, Dana-Farber Cancer Institute, 44 Binney Street, Boston, MA 02115, USA. paul_richardson@dfci.harvard.edu
Sonneveld
Pieter
P
Schuster
Michael W
MW
Irwin
David
D
Stadtmauer
Edward A
EA
Facon
Thierry
T
Harousseau
Jean-Luc
JL
Ben-Yehuda
Dina
D
Lonial
Sagar
S
San Miguel
Jesús-F
JF
Cavenagh
Jamie D
JD
Anderson
Kenneth C
KC
D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001897:Boronic Acids / Q000009:adverse effects / Q000627:therapeutic use*; D000069286:Bortezomib; D016009:Chi-Square Distribution; D003907:Dexamethasone / Q000009:adverse effects / Q000627:therapeutic use; D018450:Disease Progression; D018572:Disease-Free Survival; D005221:Fatigue / Q000139:chemically induced; D005938:Glucocorticoids / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D009101:Multiple Myeloma / Q000188:drug therapy*; D009325:Nausea / Q000139:chemically induced; D009503:Neutropenia / Q000139:chemically induced; D011719:Pyrazines / Q000009:adverse effects / Q000627:therapeutic use*; D012306:Risk; D013921:Thrombocytopenia / Q000139:chemically induced
D000970:Antineoplastic Agents; D001897:Boronic Acids; D005938:Glucocorticoids; D011719:Pyrazines; D000069286:Bortezomib; D003907:Dexamethasone