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

• Published in: BMC medicine 2014-01, Vol.12 (1), p.2-2, Article 2
• Main Authors: Huang, Xianghua, Wang, Qingwen, Chen, Wencui, Zeng, Caihong, Chen, Zhaohong, Gong, Dehua, Zhang, Haitao, Liu, Zhihong
• Format: Article
• Language: English
• Subjects: Adult; Aged; Amyloidosis - diagnosis; Amyloidosis - mortality; Amyloidosis - therapy; Analysis; Boronic Acids - administration & dosage; Bortezomib; Chemotherapy; Combined Modality Therapy; Dexamethasone - administration & dosage; Drug therapy; Female; Follow-Up Studies; Hematology; Hematopoietic Stem Cell Transplantation - methods; Hematopoietic Stem Cell Transplantation - mortality; Humans; Kidney Diseases - diagnosis; Kidney Diseases - mortality; Kidney Diseases - therapy; Liver; Male; Medical prognosis; Medical research; Medicine, Experimental; Methods; Middle Aged; Mortality; Patients; Plasma; Prospective Studies; Proteins; Pyrazines - administration & dosage; Response rates; Stem cells; Steroids; Studies; Survival Rate - trends; Transplantation, Autologous; Transplants & implants
• ISSN: 1741-7015; 1741-7015
• DOI: 10.1186/1741-7015-12-2

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. 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. 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). 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. This trial has been registered at clinicaltrials.gov with the number NCT01998503.