Induction Therapy with Bortezomib Followed by Bortezomib-High Dose Melphalan and Stem Cell Transplantation for Light Chain Amyloidosis: Results of a Prospective Clinical Trial

Abstract

The depth of hematologic response has been shown to correlate with survival and organ responses for patients with light chain (AL) amyloidosis. We conducted a prospective trial of 2 cycles of induction with bortezomib and dexamethasone on a twice a week schedule followed by conditioning with bortezomib and high-dose melphalan (HDM) and autologous stem cell transplantation (SCT). The objectives were hematologic responses, tolerability, and survival. Thirty-five patients were enrolled from 2010 to 2013. Of these, 30 proceeded with SCT, whereas 5 did not because of clinical deterioration during induction (n = 3) or complications after stem cell collection (n = 2). Two patients developed features of an autologous graft-versus-host disease-like syndrome post-SCT, which responded to steroids; no other unusual complications were seen. Treatment-related mortality occurred in 8.5% (3/35). Hematologic responses were achieved by 100% of the 27 assessable patients (63% complete response, 37% very good partial response [VGPR]) who completed the planned treatment. By intention-to-treat, hematologic responses occurred in 77% of patients (49% complete response, 29% VGPR). With a median follow-up of 36 months, the median overall survival and progression-free survival were not reached. In conclusion, incorporating bortezomib into induction and conditioning yielded a high rate of hematologic responses after HDM/SCT in patients with AL amyloidosis.

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.…”

Beyond the plasma cell: emerging therapies for immunoglobulin light chain amyloidosis

“…41 Bortezomib and dexamethasone induction for 2 cycles followed by bortezomib-high-dose melphalan conditioning for SCT resulted in a 49% hematologic CR with renal and cardiac responses at 1 year of 35% and 57%, respectively. 42 In a small, randomized trial comparing bortezomib-dexamethasone induction for 2 cycles followed by high-dose melphalan SCT to high-dose melphalan and SCT alone, the bortezomib group achieved superior hematologic CR (67.9% vs 35.7%), as well as renal responses (65.2% vs 39.1%) and cardiac responses (67% vs 25%) at 1 year. 43 In patients ineligible for SCT treated with oral melphalan and dexamethasone, CR was achieved in 37% and cardiac and renal responses in 37% and 24%.…”

Prognosztikai tényezők könnyűlánc-amyloidosisban

“…Egy prospektív vizsgálat során bortezomibbal kiegészített indukciót és konszolidációt követően ASCT-t végeztek. A betegek 100%-ában tapasztaltak hematológiai választ, ebből 63%-ban komplett remissziót, 10%-os TRM mellett [23].…”