Induction therapy with bortezomib and dexamethasone followed by autologous stem cell transplantation versus autologous stem cell transplantation alone in the treatment of renal AL amyloidosis: a randomized controlled trial

Xianghua Huang, Qingwen Wang, Wencui Chen, Caihong Zeng, Zhaohong Chen, Dehua Gong, Haitao Zhang, Zhihong Liu, Xianghua Huang, Qingwen Wang, Wencui Chen, Caihong Zeng, Zhaohong Chen, Dehua Gong, Haitao Zhang, Zhihong Liu

Abstract

Background: Although 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.

Methods: This 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.

Results: Fifty-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).

Conclusions: Our 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 registration: This trial has been registered at clinicaltrials.gov with the number NCT01998503.

Figures

Figure 1
Figure 1
Study schema.
Figure 2
Figure 2
Progression free survival and overall survival. (A) The PFS of the two groups; (B) the OS of the two groups; (C) the renal survival rates of the two groups; and (D) The OS of all patients based on the Mayo cardiac staging system.

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