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: Donna E Reece, Ute Hegenbart, Vaishali Sanchorawala, Giampaolo Merlini, Giovanni Palladini, Joan Bladé, Jean-Paul Fermand, Hani Hassoun, Leonard Heffner, Vishal Kukreti, Robert A Vescio, Lixia Pei, Christopher Enny, Dixie-Lee Esseltine, Helgi van de Velde, Andrew Cakana, Raymond L Comenzo
• Journal: Blood (Blood) Vol. 124 Issue 16 Pg. 2498-506 (Oct 16 2014) ISSN: 1528-0020 [Electronic] United States
• PMID: 25202139 (Publication Type: Clinical Trial, Phase I, Clinical Trial, Phase II, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 by The American Society of Hematology.

Chemical References

• Antineoplastic Agents
• Boronic Acids
• Pyrazines
• Bortezomib

Topics

• Adult
• Aged
• Aged, 80 and over
• Amyloidosis (drug therapy)
• Antineoplastic Agents (adverse effects, therapeutic use)
• Boronic Acids (adverse effects, therapeutic use)
• Bortezomib
• Female
• Follow-Up Studies
• Humans
• Immunoglobulin Light-chain Amyloidosis
• Male
• Middle Aged
• Pyrazines (adverse effects, therapeutic use)
• Recurrence
• Survival Analysis