Grant: Team Grant: E-Rare Joint Transnational Call

The trial aims at establishing whether the addition of the antibiotic doxycycline to bortezomib-based therapy can reduce early mortality in newly-diagnosed patients with cardiac AL amyloidosis. Cardiac involvement is responsible for almost all the early deaths in AL amyloidosis. Therapy solely aimed at the underlying disease can rescue only a minority of patients with cardiac AL amyloidosis, whose treatment remains a largely unmet need. The severity of cardiac involvement is accurately assessed by a staging system based on cardiac biomarkers. Patients with stage II/IIIa cardiac involvement will be enrolled in this study. The 6-month cumulative proportion survival of stage II/IIIa patients treated with bortezomib-based combination is approximately 75%, ranging from 67% to 79% in different series. Pre-clinical studies indicate that doxycycline 1) disrupts amyloid fibrils in vitro, 2) reduces the amyloid load in a transgenic mouse model, and 3) is capable of counteracting the proteotoxicity of amyloidogenic light chains in a C. elegans model. A recent retrospective matched case-control study showed that the addition of doxycycline to specific therapy improved survival of stage II/IIIa patients to 95%. Here we attempt to explore the utility of the agent in a prospective fashion.