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

S. W. Dubrey, 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

Research output: Contribution to journalArticlepeer-review


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.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.

Original languageEnglish
Article numberhcr105
Pages (from-to)957-970
Number of pages14
Issue number11
Publication statusPublished - Nov 2011

ASJC Scopus subject areas

  • Medicine(all)

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