Bortezomib in a phase 1 trial for patients with relapsed AL amyloidosis: cardiac responses and overall effects - PubMed (original) (raw)

Clinical Trial

. 2011 Nov;104(11):957-70.

doi: 10.1093/qjmed/hcr105. Epub 2011 Jul 13.

D E Reece, V Sanchorawala, U Hegenbart, G Merlini, G Palladini, J-P Fermand, R A Vescio, J Bladé, L T Heffner, H Hassoun, X Liu, C Enny, P Ramaswami, Y Elsayed, H Van De Velde, S Mortimer, A Cakana, R L Comenzo; Velcade Can2007 Study Group

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Clinical Trial

Bortezomib in a phase 1 trial for patients with relapsed AL amyloidosis: cardiac responses and overall effects

S W Dubrey et al. QJM. 2011 Nov.

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/m(2)) and twice-weekly (0.7, 1.0, 1.3 mg/m(2)) 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.

Conclusion: 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.

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