Bortezomib based induction followed by stem cell transplantation in light chain amyloidosis:results of the multicenter HOVON 104 trial

This prospective, multicenter, phase II study investigated the use of 4 cycles of bortezomib-dexamethasone induction treatment, followed by high dose melphalan and autologous stem cell transplantation (SCT) in patients with newly diagnosed light chain (AL) amyloidosis. The aim of the study was to improve the hematologic CR rate 6 months after SCT from 30% to 50%. Fifty patients were enrolled and 72% had 2 or more organs involved. The overall hematologic response rate after induction treatment was 80% including 20% CR and 38% VGPR. Fifteen patients did not proceed to SCT due to various reasons but mostly treatment related toxicity and disease related organ damage and death (2 patients). Thirty-one patients received melphalan 200 mg/m2 and 4 patients a reduced dose because of renal insufficiency. The SCT procedure was without treatment related mortality. Hematologic responses improved at 6 months after SCT to 86% with 46% CR and 26% VGPR. However, due to the high discontinuation rate before SCT the primary endpoint of the study was not met and the CR rate on intention to treat analysis was 32%. Organ responses continued to improve after SCT. We confirm the high efficacy of bortezomib-dexamethasone treatment in AL amyloidosis patients. However, because of both treatment related toxicity and disease characteristics, 30% of the patients could not proceed to SCT after induction treatment.