High Dose Therapy Improves Survival in Systemic Light Chain Amyloidosis

High Dose Therapy Improves Survival in Systemic Light Chain Amyloidosis

Simrit Parmar, M.D., Joshua Howell, PharmD, Michael Wang, MD, Mubeen A Khan, Qaiser Bashir, MD, Jatin J Shah, MD, Nina Shah, MD, Uday Popat, M.D., Yvonne Dinh, Sergio A Giralt, MD, Richard Champlin, MD, Robert Z. Orlowski, MD, PhD, Muzaffar Qazilbash, MD

Background: Treatment remains a challenge for systemic light chain amyloidosis (AL). Autologous stem cell transplant (AutoSCT) has been associated with long term survival. However, a recent multicenter randomized study failed to show survival benefit for AutoSCT perhaps due to high non-relapse mortality (NRM). Here we present a comparison of AutoSCT to other conventional therapies in AL patients treated at our institution with a 14-year follow up. Methods: A total of 2018 cases were identified upon pathology review from 1998-2012. AL was confirmed in 264 patients; primary amyloidosis (PA) in 147 pts and multiple myeloma with amyloidosis (AM) in 110 patients; solitary amyloidoma in 7 patients. AutoSCT was performed in 126 patients (PA=79 and AM=47). Results: The day 100 NRM was 5% and 1-year NRM was 8%. With a follow up of 14 years in surviving patients, the 10-year overall survival (OS) of AL patients was significantly better in those undergoing AutoSCT (41% vs. 17%; p<0.0001; figure 1).  Involvement of more than one organ (6-yr OS 36% vs. 55%; p=0.04) and cardiac involvement (2-yr OS of 57% vs. 78%; p=0.01) were associated with poor outcome. In the patients undergoing AutoSCT: PA vs. AM, Mayo staging, Boston University (BU) staging or bone marrow plasma cells >10 % at the time of autoSCT did not have an impact on OS. Cardiac biomarkers including NT-ProBNP and Troponin-I and T levels were available in a limited number of patients and were not analyzed for survival outcomes. In multivariate analysis, superior OS was associated with: age <60yrs (HR 2.1, p=0.022); and induction treatment before AutoSCT (HR 2.7, p=0.02). Involvement of kidney as the only end organ showed a trend toward improved survival (HR 1.6, p=0.06). Specifically for PA patients (n=79); treatment before autoSCT was associated with improved 3-yr OS: 85% vs. 66%; p=0.02. Conclusions: AL patients should be evaluated for AutoSCT and selected patients should undergo induction therapy to decrease amyloid burden prior to AutoSCT

Figure 1: OS: AutoSCt vs. Conventional Therapy in AL Amyloidosis patients

 SHAPE  \* MERGEFORMAT

Time from Diagnosis in Months

AutoSCT

Conventional Therapy

P<0.0001