Abstract
Stem cell transplantation (SCT), an effective therapy for amyloid light chain (AL) amyloidosis patients, is associated with low treatment-related mortality (TRM) with appropriate patient selection and risk-adapted dosing of melphalan (RA-SCT). Consolidation after SCT increases hematologic complete response (CR) rates and may improve overall survival (OS) for patients with <CR. We retrospectively analyzed outcomes for 143 patients who underwent RA-SCT with or without consolidation. Melphalan was administered at 100 (14%), 140 (52%) and 200 (34%) mg/m2. The TRM rate at 100 days was 5%. RA-SCT resulted in CR in 24% (3 months) and 48% (12 months) of patients. The CR rate was particularly high (62%) in patients offered bortezomib consolidation. With a median follow-up among survivors of 7.7 years, median event-free survival (EFS) with RA-SCT was 4.04 years (95% confidence interval (CI): 3.41–5.01 years); median OS was 10.4 years (95% CI: 7.3–not achieved). Patients with CR at 12 months after SCT had significantly longer EFS (P=0.01) and OS (P=0.04). In a multivariate analysis, melphalan dose had no impact on EFS (P=0.26) or OS (P=0.11). For selected patients, RA-SCT was safe and was associated with extended long-term survival. With the availability of novel agents for consolidation, RA-SCT remains a very effective and important backbone treatment for AL amyloidosis.
Highlights
High-dose melphalan plus autologous stem cell transplantation (SCT) is a standard treatment regimen for transplantation-eligible patients with systemic amyloid light chain (AL) amyloidosis
Eighty-three of the patients were treated according to one of two prospective phase 2 protocols (ClinicalTrials.gov NCT01527032 and NCT00458822), and the remaining 60 patients were treated off protocol because either they were treated before the studies were available or they had received one or two cycles of
risk-adapted melphalan plus SCT (RA-SCT) was associated with low treatment-related mortality (TRM) and, compared with other national averages,[16,17] excellent event-free survival (EFS) and overall survival (OS)
Summary
High-dose melphalan plus autologous stem cell transplantation (SCT) is a standard treatment regimen for transplantation-eligible patients with systemic amyloid light chain (AL) amyloidosis. This regimen is based on initial reports that demonstrated high hematologic response rates, including complete hematologic remissions, frequent involved organ responses and extended overall survival (OS).[1] A prospective randomized trial comparing high-dose therapy with standard dose melphalan and dexamethasone suggested that survival was better for patients who received oral chemotherapy than for those who underwent autologous SCT (56.9 vs 22.2 months; P = 0.0004).[2] These data must be interpreted with great caution, because of the 30% treatment-related mortality (TRM) rate reported,[2] highlighting the need for careful selection of patients for SCT at specialized centers. In a series of phase 2 trials, we safely administered thalidomide and dexamethasone, and bortezomib and dexamethasone, after transplantation to treatment-naive patients with newly diagnosed AL amyloidosis.[3,5] Consolidation resulted in an increased frequency of hematologic complete response (CR), which has been associated with more significant organ responses and longer OS than reported in historical controls.[6]
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