A multicenter phase 2 trial of stem cell transplantation for immunoglobulin light-chain amyloidosis (E4A97): an Eastern Cooperative Oncology Group Study

Abstract

Summary:Stem cell transplantation was introduced as a new therapeutic modality for amyloidosis. The purpose of the current study was to determine the feasibility and toxicity of stem cell transplantation for amyloidosis in a cooperative group setting in which most participating institutions would have limited experience in managing the disorder. A total of 30 patients with biopsy-proven amyloidosis shown to be immunoglobulin light-chain type were enrolled on this trial. The protocol required mobilization of a minimum of 6 Â 10 8 mononuclear cells/ kg or 5 Â 10 6 CD34 þ cells/kg ideal body weight. These targets had to be achieved within seven collections. Patients with advanced hepatic, renal, or cardiac failure were excluded. End points included objective response rate and overall survival. The secondary end point of the protocol was nonhematologic toxicity. Accrual to the study was faster than expected. The overall response rate (hematologic and organ) was 64%, with three treatmentrelated deaths. Another patient died before day 30 of sudden cardiac death not treatment related. The median follow-up of surviving patients is 30.3 months. Median survival has not been reached. Stem cell transplantation for selected patients with amyloidosis is feasible in a cooperative group setting. A multicenter phase 3 trial of high-dose therapy is indicated.

Outcome of AL amyloidosis after high-dose melphalan and autologous stem cell transplantation: long-term results in a series of 421 patients

“…6 Single and multicenter studies show CR rates of 16%-67%, organ responses in 25%-45% of patients, and a median overall survival (OS) of ϳ 5 years. [7][8][9][10][11][12][13][14][15][16] A case-control study demonstrated the benefit of this procedure for patients younger than 70 years compared with nontransplant regimens, most of them alkylator-based oral chemotherapy. 17 A major issue in HDM/SCT for AL amyloidosis is the potential for high treatment-related mortality (TRM) because of underlying organ dysfunction in this disease.…”

Treatment of light chain (AL) amyloidosis with the combination of bortezomib and dexamethasone

“…[3][4][5] Intravenous administration of high dose melphalan (HDM) supported by autologous stem cell transplantation (ASCT) significantly increased the hematologic and organ responses and improved survival, but at the expense of a treatment-related mortality rate ranging between 14% and 43% depending on the severity of the heart involvement and number of organs affected. [6][7][8][9][10][11][12][13][14][15] A risk-adapted approach has been attempted to adjust the dose of melphalan according to the patient's age and organ involvement; 12,16 with this approach early mortality is reduced but the response rate appears to be lower. 12,17 Another important advance in the treatment of AL amyloidosis was the observation that a modified schedule of high dose dexamethasone was effective in many patients with this disease.…”

Amyloidosis

“…(For example, a phase II multicenter SCT trial conducted in the United States had no patients fail to get to SCT and a 10% treatmentrelated mortality [41].) Additional problems include the fact that the response rate of oral melphalan and dexamethasone was unknown at the time the French trial was designed.…”