Aggressive Treatment Boosts Survival in AL Amyloidosis

BOSTON, Aug. 8 -- Durable remissions and prolonged survival for patients with immunoglobulin light chain amyloidosis (AL), a plasma cell dyscrasia, have been achieved with high-dose chemotherapy and autologous stem cell transplantation, investigators here reported.
Half of 80 AL patients who survived the first year after treatment had complete hematologic responses, Vaishali Sanchorawala, M.D., of Boston University, and colleagues, reported online in Blood. Median overall survival was 57 months, and median survival exceeded 10 years for patients who achieved complete responses.
For patients treated with high-dose chemotherapy and stem-cell transplantation, there was survival beyond 10 years for 23.5% of patients, compared with 2% for those treated with oral melphalan and prednisone, they wrote.
The investigators said that "the fact that the outcome is so strongly dependent upon achieving a hematologic complete response indicates that treatment response plays an important role in long-term survival."
Untreated AL amyloidosis has a median survival of 10 to 14 months, which is improved only marginally by treatment with oral melphalan and prednisone, the authors noted. Moreover, such therapy rarely results in hematologic complete response.
High-dose intravenous melphalan followed by autologous stem cell transplantation has evolved into first-line therapy for multiple myeloma because of high hematologic response rates and improved survival compared with conventional therapies. The promising outcomes in myeloma have provided a rationale for evaluating the aggressive treatment in AL amyloidosis.
Dr. Sanchorawala and colleagues reported data on 80 patients with AL amyloidosis treated since 1994 with high-dose chemotherapy and stem-cell transplantation. They defined hematologic complete response as normalization of key laboratory assessments:
Immunofixation electrophoresis of serum and urine samples
Immunohistochemical analysis of plasma cell numbers and kappa and gamma light chain expression in bone marrow biopsies
Relapse was defined as reappearance of monoclonal protein in serum or urine or clonal plasma expression in bone marrow.
All 80 patients were treated from July 1994 to July 1997, allowing for a minimum 10-year follow-up. The authors reported that 43 patients received full high-dose melphalan (200 mg/m2), and 37 received 100 to 140 mg/m2. All patients underwent stem cell mobilization with G-CSF.
The median age of the patients was 56 (range, 29-71), performance status was SWOG 1 (range; 0-3), and number of organ involvement was two (range; one to five). Thirty-eight (48%) had cardiac involvement.
Eleven patients died from complications of treatment, and five others died during stem-cell mobilization and collection, prior to initiation of high-dose chemotherapy. Six patients died of amyloidosis-related complications within the first year after treatment.
Response assessment at one year in 63 evaluable patients showed that 32 achieved complete hematologic responses. Nineteen of the 32 had received full-dose melphalan. Eleven of the 32 patients relapsed at a median time of 2.5 years.
Eighteen patients (23%) remain alive 10 years or more after treatment. Median survival has yet to be reached for patients who achieved hematologic complete responses, and 10-year survival is 53%. In contrast, patients who did not achieve a complete response had a median survival of 50 months and an estimated 10-year survival of 6% (P<0.001). Patients who received full-dose melphalan had a median survival of 71 months compared with 38 months who received lower doses.
"Efforts should continue to be directed at increasing the hematologic complete response rate," the authors concluded. "Strategies to accomplish this include the use of tandem transplantation and the use of new agents... The optimal timing and sequencing of regimens containing these agents, and comparison to or combination with one or two cycles of [high-dose melphalan and stem cell transplantation] will be determined in future trials."
The authors declared no competing interests. The study was supported in part by the National Institutes of Health and the Amyloid Research Fund at Boston University. Primary source: BloodSource reference: Sanchorawala V et al. "Long-term outcome of patients with AL amyloidosis treated with high-dose melphalan and stem cell transplantation." Blood 2007;110:epub.