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.
Keywords: AL amyloidosis; Minimal residual disease; Risk-adapted high-dose melphalan plus autologous stem cell transplantation.
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