Combined use of bortezomib, cyclophosphamide, and dexamethasone induces favorable hematological and organ responses in Japanese patients with amyloid light-chain amyloidosis: a single-institution retrospective study

Abstract

Amyloid light-chain amyloidosis (ALA) is a rare disease with poor prognosis and is often associated with monoclonal gammopathy of undetermined significance, multiple myeloma, or Waldenström macroglobulinemia. Only high-dose melphalan with auto-peripheral blood stem cell transplantation (PBSCT) has shown high long-term hematological response rates, but combinations with novel agents, including bortezomib or lenalidomide, have recently shown high hematological response rates for AL amyloidosis patients. In the present study, we treated eight Japanese patients with AL amyloidosis using bortezomib, cyclophosphamide, and dexamethasone (CyBorD). Overall response rate was 100 %; four patients (50 %) had complete remissions (CR), two (25 %) had very good partial responses, and two (25 %) had partial responses. Five of six patients (83 %) had organ responses in the heart and/or kidney. A relapsed patient repeatedly achieved CR with the CyBorD treatment. One patient died of sudden cardiac arrest a month after normalization of his serum free light chain level, which may be attributable to his spending the previous 6 months undergoing PBSCT collection and high-dose melphalan with auto-PBSCT. Altogether, the CyBorD regimen achieved high levels of hematological responses relatively quickly (within 2-3 months). The CyBorD regimen, rather than high-dose melphalan treatment, could serve as a first-line therapy for Japanese patients with ALA.

Stem cell transplantation compared with melphalan plus dexamethasone in the treatment of immunoglobulin light‐chain amyloidosis

“…22 However, treatment centers around the world apply high-dose therapy and SCT for patients with amyloidosis. [23][24][25][26] In our study, the differences in progression-free survival rates suggest that high-dose melphalan may produce a more durable response. However, the role of SCT is difficult to interpret because our patients who chose that therapy were younger, had less cardiac amyloidosis, and had a lower stage.…”

“…Data published from a European collaborative suggest that SCT is uncommon . However, treatment centers around the world apply high‐dose therapy and SCT for patients with amyloidosis . In our study, the differences in progression‐free survival rates suggest that high‐dose melphalan may produce a more durable response.…”

A mouse model recapitulating human monoclonal heavy chain deposition disease evidences the relevance of proteasome inhibitor therapy

“…This treatment was inspired by the CyBorD (cyclophosphamide, bortezomib, dexamethasone) combination, which is widely used in the various disorders associated with monoclonal gammopathies. 5,[44][45][46][47] Cyclophosphamide was shown to efficiently deplete B cells and to lower serum human gHC (supplemental Figure 4A-B), and further repeated additions of bortezomib maintained a low level of human gHC compared with nontreated mice (supplemental Figure 4B). After 5 weeks of treatment, animals were euthainzed and analyzed for kidney deposits.…”

Strength measurement of 125I seed in brachytherapy –before/during/ after implantation

“…These series have generally yielded favorable results in the setting of planned induction prior to transplant, in patients deemed ineligible for transplant, and in relapsed disease. 10,13,[23][24][25][26][27][28] Additionally, several comparative studies have also reported favorable outcomes with bortezomib-based induction. A 2014 matched case-control study of 174 newly diagnosed patients (many with advanced cardiac involvement) comparing frontline bortezomib/melphalan/dexamethasone (BMDex) with melphalan/dexamethasone (MDex) showed higher rate of CR with BMDex.…”