title: High response rate to bortezomib with or without dexamethasone in patients with relapsed or refractory multiple myeloma: results of a global phase 3b expanded access program.
abstract: Phase 2 trials have demonstrated that bortezomib +/- dexamethasone is safe and effective in relapsed multiple myeloma (MM). In this multicentre, open-label, phase 3b trial, 638 patients with relapsed or refractory MM (median 3 prior therapies) received bortezomib 1.3 mg/m2 on days 1, 4, 8, and 11 of a maximum of eight 3-week cycles (median 5 cycles). Dexamethasone 20 mg/d was added the day of and day after each bortezomib dose for progressive disease after > or =2 cycles or for stable disease after > or =4 cycles. Responses were assessed based on M-protein changes. Overall response rate was 67%, including 11% complete (100% M-protein reduction), 22% very good partial (75-99% reduction), 18% partial (50-74% reduction), and 16% minimal response (25-49% reduction). Dexamethasone was added in 208 patients (33%), of whom 70 (34%) showed improved response. Median time to best response of minimal response or better was 84 d. Most common grade 3/4 adverse events were thrombocytopenia (39%), neutropenia (16%), anaemia (12%), diarrhoea (7%), and peripheral neuropathy (6%). Neuropathy (any grade) was seen in 25% of the patients and led to discontinuation in 5%. Bortezomib, alone and combined with dexamethasone, is safe and effective in heavily pretreated patients with relapsed or refractory MM.
authors.affiliation: Princess Margaret Hospital, Toronto, Ontario, Canada. mikhael.joseph@mayo.edu
authors.forename: Joseph R
authors.initials: JR
authors.lastname: Mikhael
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Belch
authors.forename: H Miles
authors.initials: HM
authors.lastname: Prince
authors.forename: Maria Nambo
authors.initials: MN
authors.lastname: Lucio
authors.forename: Angelo
authors.initials: A
authors.lastname: Maiolino
authors.forename: Alessandro
authors.initials: A
authors.lastname: Corso
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Petrucci
authors.forename: Pellegrino
authors.initials: P
authors.lastname: Musto
authors.forename: Mieczyslaw
authors.initials: M
authors.lastname: Komarnicki
authors.forename: A Keith
authors.initials: AK
authors.lastname: Stewart
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000097:blood; D001897:Boronic Acids / Q000008:administration & dosage* / Q000627:therapeutic use; D000069286:Bortezomib; D003907:Dexamethasone / Q000627:therapeutic use*; D018450:Disease Progression; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000097:blood / Q000188:drug therapy*; D009194:Myeloma Proteins / Q000032:analysis; D011719:Pyrazines / Q000008:administration & dosage* / Q000627:therapeutic use; D012008:Recurrence; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; D001897:Boronic Acids; D009194:Myeloma Proteins; D011719:Pyrazines; C085016:multiple myeloma M-proteins; D000069286:Bortezomib; D003907:Dexamethasone