title: Long-term follow-up from a phase 1/2 study of single-agent bortezomib in relapsed systemic AL amyloidosis.
abstract: CAN2007 was a phase 1/2 study of once- and twice-weekly single-agent bortezomib in relapsed primary systemic amyloid light chain amyloidosis (AL) amyloidosis. Seventy patients were treated, including 18 and 34 patients at the maximum planned doses on the once- and twice-weekly schedules. This prespecified final analysis provides mature response and long-term outcomes data after 3-year additional follow-up since the last report. In the once-weekly 1.6 mg/m(2) and twice-weekly 1.3 mg/m(2) bortezomib groups, final hematologic response rates were 68.8% and 66.7%; 80% of patients in each group sustained their response for ≥1 year. One-year progression-free rates were 72.2% and 76.8%. Median overall survival (OS) was 62.1 months and not reached; 4-year OS rates were 75.0% and 63.0%. Low baseline difference in κ/λ free light-chain level was associated with higher hematologic complete response rates and longer OS. At data cutoff, 40 (57%) patients had received subsequent therapy, including 19 (27%) retreated with bortezomib, 11 (58%) of whom achieved complete or partial hematologic responses. Four patients received prolonged bortezomib for between 3.5 and 5.6 years, with no new safety concerns, highlighting the feasibility of long-term therapy. Single-agent bortezomib produced durable hematologic responses and promising long-term OS in relapsed AL amyloidosis. This trial was registered at www.clinicaltrials.gov as #NCT00298766.
authors.affiliation: Princess Margaret Cancer Center, Toronto, ON, Canada;
authors.forename: Donna E
authors.initials: DE
authors.lastname: Reece
authors.affiliation: Amyloidosis Center, University of Heidelberg, Heidelberg, Germany;
authors.forename: Ute
authors.initials: U
authors.lastname: Hegenbart
authors.affiliation: Boston University Medical Center, Boston, MA;
authors.forename: Vaishali
authors.initials: V
authors.lastname: Sanchorawala
authors.affiliation: Amyloidosis Research and Treatment Center, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico, Policlinico San Matteo, Department of Molecular Medicine, University of Pavia, Pavia, Italy;
authors.forename: Giampaolo
authors.initials: G
authors.lastname: Merlini
authors.affiliation: Amyloidosis Research and Treatment Center, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico, Policlinico San Matteo, Department of Molecular Medicine, University of Pavia, Pavia, Italy;
authors.forename: Giovanni
authors.initials: G
authors.lastname: Palladini
authors.affiliation: Hematology Department, Institute of Hematology and Oncology, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Hospital Clínic, University of Barcelona, Barcelona, Spain;
authors.forename: Joan
authors.initials: J
authors.lastname: Bladé
authors.affiliation: Hôpital Saint Louis, Paris, France;
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Fermand
authors.affiliation: Memorial Sloan-Kettering Cancer Center, New York, NY;
authors.forename: Hani
authors.initials: H
authors.lastname: Hassoun
authors.affiliation: Hematology and Medical Oncology, Winship Cancer Institute of Emory University, Atlanta, GA;
authors.forename: Leonard
authors.initials: L
authors.lastname: Heffner
authors.affiliation: Princess Margaret Cancer Center, Toronto, ON, Canada;
authors.forename: Vishal
authors.initials: V
authors.lastname: Kukreti
authors.affiliation: Cedars-Sinai Medical Center, Los Angeles, CA;
authors.forename: Robert A
authors.initials: RA
authors.lastname: Vescio
authors.affiliation: Janssen Research and Development, LLC, Raritan, NJ;
authors.forename: Lixia
authors.initials: L
authors.lastname: Pei
authors.affiliation: Janssen Research and Development, LLC, Raritan, NJ;
authors.forename: Christopher
authors.initials: C
authors.lastname: Enny
authors.affiliation: Takeda Pharmaceuticals International Co., Cambridge, MA;
authors.forename: Dixie-Lee
authors.initials: DL
authors.lastname: Esseltine
authors.affiliation: Janssen Research and Development, Division of Janssen Pharmaceutica NV, Beerse, Belgium;
authors.forename: Helgi
authors.initials: H
authors.lastname: van de Velde
authors.affiliation: Janssen Research and Development, High Wycombe, United Kingdom; and.
authors.forename: Andrew
authors.initials: A
authors.lastname: Cakana
authors.affiliation: Tufts Medical Center, Boston, MA.
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*; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001897:Boronic Acids / Q000009:adverse effects / Q000627:therapeutic use*; D000069286:Bortezomib; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D000075363:Immunoglobulin Light-chain Amyloidosis; D008297:Male; D008875:Middle Aged; D011719:Pyrazines / Q000009:adverse effects / Q000627:therapeutic use*; D012008:Recurrence; D016019:Survival Analysis
chemical_list: D000970:Antineoplastic Agents; D001897:Boronic Acids; D011719:Pyrazines; D000069286:Bortezomib