Efficacy and safety of once-weekly and twice-weekly bortezomib in patients with relapsed systemic AL amyloidosis: Results of a phase 1/2 study Journal Article
| Authors: | Reece, D. E.; Hegenbart, U.; Sanchorawala, V.; Merlini, G.; Palladini, G.; Blade, J.; Fermand, J. P.; Hassoun, H.; Heffner, L.; Vescio, R. A.; Liu, K.; Enny, C.; Esseltine, D. L.; van de Velde, H.; Cakana, A.; Comenzo, R. L. |
| Article 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/m2once-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. © 2011 by The American Society of Hematology. |
| Keywords: | adult; treatment response; aged; survival rate; major clinical study; overall survival; dose response; drug dose reduction; drug efficacy; drug safety; drug withdrawal; progression free survival; bortezomib; multiple cycle treatment; phase 2 clinical trial; peripheral neuropathy; relapse; creatinine; amyloidosis; drug dose escalation; dosage schedule comparison; interstitial lung disease; phase 1 clinical trial; protein urine level; brain natriuretic peptide; creatinine clearance; amino terminal pro brain natriuretic peptide; acute heart failure; heart ventricle hypertrophy |
| Journal Title: | Blood |
| Volume: | 118 |
| Issue: | 4 |
| ISSN: | 0006-4971 |
| Publisher: | American Society of Hematology |
| Date Published: | 2011-07-28 |
| Start Page: | 865 |
| End Page: | 873 |
| Language: | English |
| DOI: | 10.1182/blood-2011-02-334227 |
| PROVIDER: | scopus |
| PUBMED: | 21562045 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 1" - "Export Date: 3 October 2011" - "CODEN: BLOOA" - "Source: Scopus" |
