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- Title
Bortezomib in a phase 1 trial for patients with relapsed AL amyloidosis: cardiac responses and overall effects.
- Authors
Dubrey, S.W.; Reece, D.E.; Sanchorawala, V.; Hegenbart, U.; Merlini, G.; Palladini, G.; Fermand, J.-P.; Vescio, R.A.; Bladé, J.; Heffner, L.T.; Hassoun, H.; Liu, X.; Enny, C.; Ramaswami, P.; Elsayed, Y.; Van De Velde, H.; Mortimer, S.; Cakana, A.; Comenzo, R.L.
- Abstract
Background: Bortezomib is approved for the treatment of multiple myeloma and a role has been suggested in the treatment of systemic AL amyloidosis (AL).Methods: In this phase 1 dose-escalation portion of the first prospective study of single-agent bortezomib in AL, 31 patients with relapsed disease, including 14 (45%) with cardiac involvement, received bortezomib in seven dose cohorts on once-weekly (0.7, 1.0, 1.3, 1.6 mg/m2) and twice-weekly (0.7, 1.0, 1.3 mg/m2) schedules. Electrocardiographic, Holter and echocardiographic studies were evaluated in all patients to determine safety and response.Results: During therapy (median treatment period 210 days), no patient developed significant ventricular or supraventricular rhythm disturbance on 24-h Holter monitoring; however, no patient satisfied study criteria for cardiac response using echocardiographic assessment or New York Heart Association classification. Seven patients (23%) had a ≥10% fall in left ventricular ejection fraction, but only one met criteria for cardiac deterioration. The predominant cardiac adverse events were peripheral edema (23%), orthostatic hypotension (13%) and hypotension (10%). Two patients developed grade 3 congestive heart failure, which resolved following treatment interruption. In this Phase 1 portion, the maximum tolerated dose of bortezomib on either schedule was not reached. Hematologic responses occurred in 14 patients (45%), including seven (23%) complete responses. In non-responders mean left ventricular wall thickness increased during the course of treatment.Conclusions: AL is frequently rapidly progressive; in these patients who had relapsed or progressed following previous conventional therapies, these results suggest that bortezomib may slow the progression of cardiac amyloid with limited toxicity.
- Subjects
MULTIPLE myeloma treatment; CARDIAC amyloidosis; ELECTROCARDIOGRAPHY; DISEASE relapse; DISEASE progression; CLINICAL trials; ORTHOSTATIC hypotension
- Publication
QJM: An International Journal of Medicine, 2011, Vol 104, Issue 11, p957
- ISSN
1460-2725
- Publication type
Article