Abstract
BackgroundAlthough the use of bortezomib alone and in combination with steroids has shown efficacy in AL amyloidosis, its role in combination with high-dose melphalan and autologous stem cell transplantation (HDM/SCT) is unknown. In this study, we evaluated bortezomib in combination with dexamethasone (BD) for induction chemotherapy prior to HDM/SCT.MethodsThis was a single-center, prospective, randomized controlled trial comparing induction therapy consisting of two BD cycles followed by HDM/SCT (BD + HDM/SCT) with HDM/SCT alone in the treatment of patients with newly diagnosed AL amyloidosis. The hematological and organ responses of the patients were assessed every three months post HDM/SCT.ResultsFifty-six patients newly diagnosed with renal (100%), cardiac (57.1%), liver (7.1%), or nervous system (8.9%) AL amyloidosis were enrolled in this study; 28 patients were assigned to each arm. Two patients died within 100 days of HDM/SCT (3.6% treatment-related mortality). The overall hematologic response rates in the BD + HDM/SCT arm and HDM/SCT arm at three, six and twelve months were 78.5% versus 50%, 82.1% versus 53.5% and 85.7% versus 53.5%, respectively. In the BD + HDM/SCT arm, 15 (53.5%) patients achieved a hematologic response after BD and before HDM/SCT. An intention-to-treat analysis revealed a higher rate of complete remission in the BD + HDM/SCT arm at both 12 and 24 months (67.9% and 70%, respectively) than with the HDM/SCT-only therapy (35.7% and 35%, respectively, P = 0.03). After a median follow-up of 28 months, the survival rates at 24 months post-treatment start were 95.0% in the BD + HDM/SCT group and 69.4% in the HDM/SCT alone group (P = 0.03).ConclusionsOur preliminary data suggest that the outcome of treating AL amyloidosis with BD induction and HDM/SCT was superior to the outcome of the HDM/SCT treatment alone.Trial registrationThis trial has been registered at clinicaltrials.gov with the number NCT01998503.
Highlights
The use of bortezomib alone and in combination with steroids has shown efficacy in AL amyloidosis, its role in combination with high-dose melphalan and autologous stem cell transplantation (HDM/SCT) is unknown
To determine whether induction therapy with bortezomib combined with dexamethasone (BD) is advantageous in patients with AL amyloidosis, we prospectively evaluated a therapeutic regimen consisting of two cycles of BD chemotherapy followed by HDM/SCT in a single-center study
All patients had amyloid disease, which was confirmed by renal biopsy and documented plasma cell dyscrasia; the AL amyloidosis diagnosis and the assessment of organ involvement were based on consensus criteria [26]
Summary
The use of bortezomib alone and in combination with steroids has shown efficacy in AL amyloidosis, its role in combination with high-dose melphalan and autologous stem cell transplantation (HDM/SCT) is unknown. Melphalan (MEL) and prednisone administration was the first effective regimen developed for AL amyloidosis; the treatment responses are typically slow and rarely result in complete remission [6,7]. An Italian study combining MEL with high-dose dexamethasone (MDex) noted an impressive hematologic response rate of 67% [8] and long-term remissions in AL amyloidosis [9], and MDex is still considered a standard for non-study, non-transplant intervention because of its low toxicity profile [10]. Intensive therapy with highdose MEL and autologous stem cell transplantation (HDM/SCT) is effective in AL amyloidosis and can offer durable remission in some patients [11,12]. It is necessary to identify modifications to the HDM/SCT procedure that could improve outcomes in patients with AL amyloidosis
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