title: Efficacy and safety of once-weekly and twice-weekly bortezomib in patients with relapsed systemic AL amyloidosis: results of a phase 1/2 study.
abstract: This first prospective phase 2 study of single-agent bortezomib in relapsed primary systemic AL amyloidosis evaluated the recommended (maximum planned) doses identified in phase 1 testing (1.6 mg/m² once weekly [days 1, 8, 15, and 22; 35-day cycles]; 1.3 mg/m² twice weekly [days 1, 4, 8, and 11; 21-day cycles]). Among all 70 patients enrolled in the study, 44% had ≥ 3 organs involved, including 73% and 56% with renal and cardiac involvement. In the 1.6 mg/m² once-weekly and 1.3 mg/m² twice-weekly groups, the hematologic response rate was 68.8% and 66.7% (37.5% and 24.2% complete responses, respectively); median time to first/best response was 2.1/3.2 and 0.7/1.2 months, and 78.8% and 75.5% had response durations of ≥ 1 year, respectively. One-year hematologic progression-free rates were 72.2% and 74.6%, and 1-year survival rates were 93.8% and 84.0%, respectively. Outcomes appeared similar in patients with cardiac involvement. Among all 70 patients, organ responses included 29% renal and 13% cardiac responses. Rates of grade ≥ 3 toxicities (79% vs 50%) and discontinuations/dose reductions (38%/53% vs 28%/22%) resulting from toxicities appeared higher with 1.3 mg/m² twice-weekly versus 1.6 mg/m² once-weekly dosing. Both bortezomib dose schedules represent active, well-tolerated regimens in relapsed AL amyloidosis. This study was registered at www.clinicaltrials.gov as #NCT00298766.
authors.affiliation: Princess Margaret Hospital, Toronto, ON, Canada. Donna.Reece@uhn.on.ca
authors.forename: Donna E
authors.initials: DE
authors.lastname: Reece
authors.forename: Ute
authors.initials: U
authors.lastname: Hegenbart
authors.forename: Vaishali
authors.initials: V
authors.lastname: Sanchorawala
authors.forename: Giampaolo
authors.initials: G
authors.lastname: Merlini
authors.forename: Giovanni
authors.initials: G
authors.lastname: Palladini
authors.forename: Joan
authors.initials: J
authors.lastname: Bladé
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Fermand
authors.forename: Hani
authors.initials: H
authors.lastname: Hassoun
authors.forename: Leonard
authors.initials: L
authors.lastname: Heffner
authors.forename: Robert A
authors.initials: RA
authors.lastname: Vescio
authors.forename: Kevin
authors.initials: K
authors.lastname: Liu
authors.forename: Christopher
authors.initials: C
authors.lastname: Enny
authors.forename: Dixie-Lee
authors.initials: DL
authors.lastname: Esseltine
authors.forename: Helgi
authors.initials: H
authors.lastname: van de Velde
authors.forename: Andrew
authors.initials: A
authors.lastname: Cakana
authors.forename: Raymond L
authors.initials: RL
authors.lastname: Comenzo
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000686:Amyloidosis / Q000188:drug therapy*; D001897:Boronic Acids / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D000069286:Bortezomib; D005260:Female; D006801:Humans; D000075363:Immunoglobulin Light-chain Amyloidosis; D008297:Male; D008875:Middle Aged; D011480:Protease Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D011719:Pyrazines / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D012008:Recurrence
chemical_list: D001897:Boronic Acids; D011480:Protease Inhibitors; D011719:Pyrazines; D000069286:Bortezomib