title: Safety and efficacy of bortezomib in high-risk and elderly patients with relapsed multiple myeloma.
abstract: 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.
authors: Medical Oncology, Dana-Farber Cancer Institute, 44 Binney Street, Boston, MA 02115, USA. paul_richardson@dfci.harvard.edu
authors: Paul G
authors: PG
authors: Richardson
authors: Pieter
authors: P
authors: Sonneveld
authors: Michael W
authors: MW
authors: Schuster
authors: David
authors: D
authors: Irwin
authors: Edward A
authors: EA
authors: Stadtmauer
authors: Thierry
authors: T
authors: Facon
authors: Jean-Luc
authors: JL
authors: Harousseau
authors: Dina
authors: D
authors: Ben-Yehuda
authors: Sagar
authors: S
authors: Lonial
authors: Jesús-F
authors: JF
authors: San Miguel
authors: Jamie D
authors: JD
authors: Cavenagh
authors: Kenneth C
authors: KC
authors: Anderson
mesh_terms: 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
chemical_list: D000970:Antineoplastic Agents; D001897:Boronic Acids; D005938:Glucocorticoids; D011719:Pyrazines; D000069286:Bortezomib; D003907:Dexamethasone