Outcome of Patients with Systemic Light Chain (AL) Amyloidosis with Concurrent Renal and Cardiac Involvement

Background: Light chain amyloidosis (AL) involves deposition of misfolded amyloid fibrils in the affected organs, including heart and kidneys, causing organ dysfunction.  We sought to determine if the concurrent cardiac and renal involvement was associated with a worse outcome than either organ alone.

Methods: We identified 129 patients (pts) with AL who received high-dose chemotherapy followed by autologous hematopoietic stem cell transplantation (auto-HCT) at our institution between 1997 and 2014.  Ninety nine patients had either renal (group 1: n=62, 62%), cardiac (group 2: n=20, 20%) or both renal and cardiac (group 3, n=17, 17%) involvement. Hematologic response (HR) was defined according to the international myeloma working group (IMWG) criteria and organ response (OR) was defined according to consensus opinion from the 10^th international symposium on amyloid and amyloidosis (M Gertz et al. Am J Hematol. 2005 Aug; 79[4]:319-28).

Results: The median age at auto-HCT for groups 1, 2 and 3 was 58, 60, and  53 years, respectively (p= 0.30). The median urine protein in groups 1, 2 and 3 was 5.5, 0.28 and 2.0 g/24h , respectively(p= <0.0001). The medain difference in involved and uninvolved free light chain(dFLC) in groups 1, 2 and 3 was 37, 147 and 128, respectively (p= 0.10). The medain NT-Pro BNP (pg/ml) in groups 2 and 3 was 1206 and 1766, respectively (p= 1.0), and median intraventricular septal thickness (cm) was 1.3 and 1.4, respectively (p= 0.87). Mayo Cardiac stages for patients in groups 2 and 3 were: stage 1; 4 (11%), stage 2; 13 (35%),  stage 3; 7 (19%) and unavailable; 13 (35%).The median time from diagnosis to auto-HCT in groups 1, 2 and 3 was 7 (2-120), 8 (3-35) and 6 (3-96) months, respectively . The overall hematological response rate (CR+VGPR+PR) in groups 1, 2 and 3  was 75%, 87.5% and 82% respectively (p= 0.38). Organ response in groups 1, 2 and 3 was 40%, 40% and 70% respectively (p= 0.002). Four (6%) patients in group 1, 0 in group 2 and 1 (6%) patient in group 3 died of non-relapse causes (NRM) in the first 100 days (p= 0.66). The median progression free survival (PFS) from auto-HCT in groups 1, 2 and 3 was not reached , 19.5 months, and 21 months respectively (p= 0.035) (Fig 1A). The median overall survival (OS) in groups 1, 2 and 3 was 10, 4.3 and 5 years, respectively (p= 0.035) (Fig 1B). In a landmark analysis for patient who were alive and in HR at 1 year post auto-HCT, the median PFS  in groups 1-3 was not reached, 37.5 and 21 months, respectively (p= 0.16) (Fig 1C).

Conclusion: Patients with concurrent cardiac and renal AL have similar PFS and OS as patients with cardiac AL alone, but worse than patients with renal AL only. These patients may potentially benefit from auto-HCT.