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Clinical Trial
. 2019 Nov;104(11):2274-2282.
doi: 10.3324/haematol.2018.213900. Epub 2019 Mar 28.

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

Monique C Minnema  1 , Kazem Nasserinejad  2 , Bouke Hazenberg  3 , Ute Hegenbart  4 , Philip Vlummens  5 , Paula F Ypma  6 , Nicolaus Kröger  7 , Ka Lung Wu  8 , Marie Jose Kersten  9 , M Ron Schaafsma  10 , Sandra Croockewit  11 , Esther de Waal  12 , Sonja Zweegman  13 , Lidwien Tick  14 , Annemieke Broijl  15 , Harry Koene  16 , Gerard Bos  17 , Pieter Sonneveld  15 , Stefan Schönland  4
Affiliations
Clinical Trial

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

Monique C Minnema et al. Haematologica. 2019 Nov.

Abstract

This prospective, multicenter, phase II study investigated the use of four cycles of bortezomib-dexamethasone induction treatment, followed by high-dose melphalan and autologous stem cell transplantation (SCT) in patients with newly diagnosed light chain amyloidosis. The aim of the study was to improve the hematologic complete remission (CR) rate 6 months after SCT from 30% to 50%. Fifty patients were enrolled and 72% had two or more organs involved. The overall hematologic response rate after induction treatment was 80% including 20% CR and 38% very good partial remissions (VGPR). Fifteen patients did not proceed to SCT for 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 four patients a reduced dose because of renal function impairment. There were no deaths related to the transplantation procedure. Hematologic responses improved at 6 months after SCT to 86% with 46% CR and 26% VGPR. However, due to the high treatment discontinuation rate before transplantation the primary endpoint of the study was not met and the CR rate in the intention-to-treat analysis was 32%. Organ responses continued to improve after SCT. We confirm the high efficacy of bortezomib-dexamethasone treatment in patients with AL amyloidosis. However, because of both treatment-related toxicity and disease characteristics, 30% of the patients could not proceed to SCT after induction treatment. (Trial registered at Dutch Trial Register identifier NTR3220).

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Figures

Figure 1.
Figure 1.
Consolidated Standards of Reporting Trials (CONSORT) diagram of the 50 patients included in the trial. HDM: high-dose melphalan; G-CSF: granulocyte colony-stimulating factor.
Figure 2.
Figure 2.
Response rates following the initiation of treatment. The upper line represents the time to first response, defined as partial response or better, while the lower line represents the time to first complete response. PR: partial response; CR: complete response.
Figure 3.
Figure 3.
Organ responses depicted separately for patients who proceeded to autologous stem cell transplantation or not. Organ responses were assessed according to consensus criteria after induction and as best responses achieved during study treatment and follow-up. Auto-SCT: autologous stem cell transplantation.
Figure 4.
Figure 4.
Overall and progression-free survival of the total cohort of patients and the 35 patients who underwent autologous stem cell transplantation. (A) Progression-free and overall survival from date of registration in the trial for the 50 patients included. (B) Progression-free survival from autologous stem cell transplantation of the 35 transplanted patients according to response achieved after induction therapy. PFS: progression-free survival; OS: overall survival; PR: partial remission; VGPR: very good partial remission.
See this image and copyright information in PMC

References

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