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

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.

Autologous hematopoietic stem cell transplantation in light chain amyloidosis (AL) with renal involvement

“…13 Some more recent studies, however, support the role of PI or IMiD-based induction in improving outcomes after auto-HCT. 12 The significance of reduction of FLC as a predictor of survival was first reported by Dispenzieri et al 14 A recent report from the National Amyloidosis Center in the United Kingdom identified the magnitude of the FLC response at 6 months from baseline as a strong predictor of PFS and OS. 15 HD melphalan is nephrotoxic, and some studies have reported a high risk of renal toxicity.…”

“…Huang et al 12 conducted a randomized clinical trial where patients either received induction with bortezomib+dexametha-sone or no induction before HD melphalan and auto-HCT. Renal response at 2 years was 75% in the induction arm and 53% in the non-induction arm.…”

Outcomes of autologous hematopoietic cell transplantation in primary amyloidosis after bortezomib-based induction therapy

“…5,6 Treatment with bortezomib pre-AHCT has been shown to improve transplant eligibility for patients, previously considered to be too high risk for AHCT, and may increase the response rates following AHCT. [7][8][9][10] Herein, we describe our experience using bortezomib prior to AHCT and demonstrate the feasibility of this approach.…”

“…[8][9][10]15 Overall, the collective experience of bortezomibbased induction prior to AHCT shows that it is a feasible approach for most patients who are otherwise candidates for transplantation and leads to favorable long-term outcomes.…”

“…Three patients with known Table 2. Summary of studies of bortezomib-based induction treatment prior to AHCT Sanchorawala et al 6 Cornell et al 8 Scott et al 9 Huang et al 10 Current study Abbreviations: AHCT = autologous hematopoietic cell transplant; Bor-Dex = bortezomib + dexamethasone; CyBorD = cyclophosphamide + bortezomib + dexamethasone; ORR = overall response rate; OS = overall survival; TRM = treatment related mortality; VGPR = very good partial response.…”