Treatment of AL Amyloidosis: Less Is More

Summary and Comment |
September 12, 2007

Treatment of AL Amyloidosis: Less Is More

  1. Michael E. Williams, MD

Patients with AL amyloidosis survived longer when they were treated with conventional-dose melphalan plus dexamethasone versus high-dose melphalan followed by autologous stem-cell transplantation.

  1. Michael E. Williams, MD

Immunoglobin-light-chain–related (AL) amyloidosis, in which monoclonal immunoglobulin light chains are deposited in tissues as amyloid, is incurable with available therapies. Survival after diagnosis typically is short, due to organ dysfunction and failure. Results of previous studies have suggested that dose-intensive chemotherapy with melphalan (Alkeran) followed by autologous stem-cell transplantation (ASCT) lengthens survival, albeit with high transplant-related mortality.

In a prospective multicenter French clinical trial, researchers compared standard-dose oral melphalan plus pulsed dexamethasone with high-dose intravenous melphalan plus ASCT in patients with biopsy-proven AL amyloidosis. Patients with symptomatic concurrent multiple myeloma were excluded, and no more than two courses of chemotherapy were permitted prior to enrollment; median time from diagnosis to randomization was 48 days. Hematologic responses, quantitative serum light-chain levels, and organ function were assessed.

Fifty patients were enrolled in each group, although 13 who were assigned to ASCT did not undergo transplantation (due to early death, inadequate stem-cell harvest, or patient refusal). Nine of 37 patients (24%) who underwent ASCT died within 100 days. In the melphalan-plus-dexamethasone (M/D) group, two early deaths and five late deaths occurred before day 130. M/D patients received a median of 12 cycles (range, 0–25) of therapy. Hematologic and organ-function responses were similar in the two groups. In intent-to-treat analysis, median overall survival was 56.9 months in the M/D arm and 22.2 months in the ASCT arm (P=0.04). In a per-protocol analysis that was performed in patients who survived for 6 months or longer and who received their assigned treatment (28 ASCT and 37 M/D patients), no significant survival advantage was observed for either therapy.


The results of this multicenter study show no benefit for high-dose therapy plus stem-cell transplantation over conventional therapy with melphalan plus dexamethasone; in fact, survival was significantly shorter in the former group. Transplant-related mortality after ASCT in this study was similar to that in other amyloid transplant studies, and, as such, does not seem to account for the inferior outcome. Although the rationale for performing ASCT — to achieve complete remission and eliminate monoclonal light-chain production to abolish or minimize ongoing amyloid deposition — makes sense, such a benefit was not evinced by this trial.


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