Pilot Study of Bortezomib and Dexamethasone Pre- and Post-Risk-Adapted Autologous Stem Cell Transplantation in AL Amyloidosis

• Published in: Biology of blood and marrow transplantation 2020-01, Vol.26 (1), p.204-208
• Main Authors: Landau, Heather, Lahoud, Oscar, Devlin, Sean, Lendvai, Nikoletta, Chung, David J., Dogan, Ahmet, Landgren, C. Ola, Giralt, Sergio, Hassoun, Hani
• Format: Article
• Language: English
• Subjects: Adult; Aged; AL amyloidosis; Autografts; Bortezomib - administration & dosage; Bortezomib - adverse effects; Dexamethasone - administration & dosage; Dexamethasone - adverse effects; Disease-Free Survival; Female; Follow-Up Studies; Humans; Immunoglobulin Light-chain Amyloidosis - blood; Immunoglobulin Light-chain Amyloidosis - mortality; Immunoglobulin Light-chain Amyloidosis - therapy; Male; Middle Aged; Minimal residual disease; Neoplasm, Residual; Pilot Projects; Prospective Studies; Risk Factors; Risk-adapted high-dose melphalan plus autologous stem cell transplantation; Stem Cell Transplantation; Survival Rate
• ISSN: 1083-8791; 1523-6536
• DOI: 10.1016/j.bbmt.2019.08.016

•We analyzed treatment with bortezomib and dexamethasone before and after risk-adapted autologous stem cell transplantation.•This comprehensive 3-phase regimen is safe for the upfront management of AL amyloidosis.•We report deep (including minimal residual disease-negative), durable remissions promoting organ recovery. Treatment for AL amyloidosis aims to eradicate clonal plasma cells, thereby disrupting the amyloid deposition causing organ damage. Risk-adapted high-dose melphalan plus autologous stem cell transplantation (RA-ASCT) is an effective therapy. We conducted a prospective pilot analysis of a comprehensive approach using bortezomib and dexamethasone (BD) before and after RA-ASCT in 19 patients. BD induction (up to 3 cycles of bortezomib 1.3 mg/m2 i.v. and dexamethasone 40 mg orally [p.o.] or i.v. on days 1, 4, 8, and 11) was followed by RA-ASCT and then BD consolidation (6 cycles of bortezomib 1.3 mg/m2i.v. and dexamethasone 20 mg p.o. or i.v. weekly for 4 weeks, every 12 weeks). The overall hematologic response rate (partial response or better) was 95%, including 37% minimal residual disease negative [MRD(-)] complete response (CR) by flow cytometry (sensitivity up to 1/106 cells). At 2 years, progression-free survival (PFS) and overall survival were 68% (95% confidence interval [CI], 50% to 93%) and 84% (95% CI, 69% to 99%), respectively, with median duration of follow-up in survivors of 61 months (range, 42 to 84 months). In a landmark analysis, patients achieving MRD(-) CR had superior PFS (P= .008). This approach is safe and yields deep and durable remissions promoting organ recovery. Each treatment phase deepened the response. Future aims include improving the efficacy and toxicity of each phase.