Induction Therapy with Bortezomib and Dexamethasone Followed By Autologous Stem Cell Transplantation for Systemic Light Chain Amyloidosis: Our Experience

Introduction: The optimal treatment approach for systemic AL amyloidosis remains unclear. Autologous stem cell transplant (ASCT) is the only modality associated with long term survival, but failure to show survival benefit in randomized clinical trial raises doubts about its efficacy ^{1, 2}. Outcomes after ASCT are better in patients who achieve complete hematologic response after the ASCT³. One report has shown improved outcomes with combining one dose of the proteasome inhibitor bortezomib with high dose melphalan as part of conditioning regimen ⁴. Preliminary data from a recent study suggest that the outcome of treating AL amyloidosis with two cycles of bortezomib and dexamethasone followed by ASCT was superior to the outcome of the ASCT alone⁵. We describe our experience with giving 4-6 cycles of bortezomib and dexamethasone induction prior to high dose melphalan and ASCT in patients with systemic AL amyloidosis.

Patients and methods: We included all patients who underwent autologous transplant for symptomatic systemic AL amyloidosis at our institution from October 2010 till June 2014. Five patients were included in the analysis and patient characteristics are described in table 1. All patient received 4 -6 cycles of induction with bortezomib and dexamethasone followed by autologous stem cell transplant using high dose melphalan (200 mg/m²). One patient also received six cycles of lenalidomide and dexamethasone prior to bortezomib based induction for lack of response. Hematologic and organ response were assessed using the definitions from the 10^th International symposium on Amyloid and Amyloidosis. Overall survival was calculated by Kaplan Meyer’s method using Graphpad Prism 6.0 software.

Results: There was no transplant related mortality. After median follow up of 13 months (12-25 months) all patient are alive. Toxicities from the ASCT were mostly cytopenias in the immediate post-transplant period which were managed as per the standard of care. Two patients achieved hematological complete response while one more had very good partial response and other two achieved partial response. Of the four patients with nephrotic range proteinuria, two patients had > 95% reduction in proteinuria, one had > 75% reduction in proteinuria and another patient had > 50% reduction in proteinuria. One patient had Liver involvement with elevated alkaline phosphatase which normalized post-transplant (table 2). The responses were maintained on last follow up and none of the patient had hematological or organ relapses.

Discussion: Bortezomib alone and in combination with steroids has shown efficacy in AL amyloidosis, but its role in induction prior to high dose melphalan/ASCT to help achieve deeper hematological response is unknown. Our experience shows that this combination may be highly efficacious without significant toxicity. Limitations of our study include the small number of patients and absence of any patients with cardiac involvement, which is a worse prognostic marker. We conclude that the bortezomib and dexamethasone induction followed by high dose melphalan/ASCT for AL amyloidosis should be studied in prospective trials.