Long-term follow-up from a phase 1/2 study of single-agent bortezomib in relapsed systemic AL amyloidosis Journal Article
| Authors: | Reece, D. E.; Hegenbart, U.; Sanchorawala, V.; Merlini, G.; Palladini, G.; Bladé, J.; Fermand, J. P.; Hassoun, H.; Heffner, L.; Kukreti, V.; Vescio, R. A.; Pei, L.; Enny, C.; Esseltine, D. L.; van de Velde, H.; Cakana, A.; Comenzo, R. L. |
| Article 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 1.6mg/m2 and twice-weekly 1.3mg/m2 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. |
| Keywords: | adult; major clinical study; overall survival; lenalidomide; prednisone; thalidomide; disease course; cisplatin; doxorubicin; drug safety; treatment duration; treatment planning; outcome assessment; follow up; progression free survival; bortezomib; multiple cycle treatment; phase 2 clinical trial; etoposide; relapse; bendamustine; cyclophosphamide; dexamethasone; melphalan; amyloidosis; light chain; stem cell transplantation; cause of death; multicenter study; drug response; long term care; phase 1 clinical trial; drug dose increase; drug dose regimen; immunoglobulin kappa chain; immunoglobulin lambda chain; neurologic disease; hematologic disease; amyloid protein; new drug; human; male; female; article; amyloid long chain amyloidosis |
| Journal Title: | Blood |
| Volume: | 124 |
| Issue: | 16 |
| ISSN: | 0006-4971 |
| Publisher: | American Society of Hematology |
| Date Published: | 2014-10-16 |
| Start Page: | 2498 |
| End Page: | 2506 |
| Language: | English |
| DOI: | 10.1182/blood-2014-04-568329 |
| PROVIDER: | scopus |
| PMCID: | PMC4199951 |
| PUBMED: | 25202139 |
| DOI/URL: | |
| Notes: | Export Date: 1 December 2014 -- Source: Scopus |
