Patterns of Treatment Failure in Systemic Light Chain Amyloidosis with Long-Term Survival after Chemotherapy
Authors: Kim Hee Kyung , Kim Kihyun , Hansang Lee , Mi Hwa Heo , Silvia Park 
Published: October 2019

Abstract
Background
The prognosis of systemic light chain (AL) amyloidosis is poor, which is associated early death assiated with cardiac involvement. It was reported that patients who avoided earth death have better survival than myeloma patients. However, the patterns of treatment failure of AL amyloidosis patients with long-term survival have not been evaluated. The aim of this study was to analyze the clinical outcome of patients with AL amyloidosis who survived more than 1 year and experienced treatment failure after systemic chemotherapy.
Methods
In this retrospective cohort study, 165 patients with AL amyloidosis received chemotherapy including ASCT in Samsung medical center between September 1997 and September 2015 were analyzed. The conditioning chemotherapy of ASCT was high-dose melphalan (200mg/m2). The patients who survived more than 1 year and showed disease progression or death were included in the study population. Progression was defined as first hematologic or organ progression after diagnosis of systemic amyloidosis. Hematologic or organ progression was evaluated according to the Roundtable on Clinical Research in Immunoglobulin Light-chain Amyloidosis. The progression-free survival and overall survival were analyzed.
Results
A total of 112 patients who survived more than 1 year during the study period with median follow-up 50.3 months, 7 patients was lost to follow-up and 47 patients did not showed progression. 58 patients experienced death or progression and they were eligible for analysis. 14 of 58 (24.1%) patients received ASCT, 13 (22.4%) patients received bortezomib-based regimens, 6 (10.3%) patients received oral melphalan with dexamethasone before progression. 4 (6.9%) patients achieved hematologic complete remission (CR) and 5 (8.6%) patients achieved hematologic very good partial response (VGPR), all of 9 patients demonstrated cardiac progresion. Otherwise, 27 of 47 patients (57.4%) without progression achieved hematologic CR or VGPR. Among 54 patients who did not achieve hematologic CR, 24 (44.4 %) patients showed hematologic progression and 28 (51.9%) patients showed cardiac progression, kidney progression was 17 (31.5%) and liver progression was 3 (5.6%), respectively. There were 4 patients with hematologic progression followed by cardiac progression, and the median time interval from hematologic progression to cardiac progression was 2.6 months. 39 deaths (67.2%) were identified in cohort and most common cause of death was cardiac progression (12 of 39 deaths - heart failure, fatal arrhythmia, cardiac arrest).
Conclusion
More than half of patients in this cohort received ASCT or bortezomib based chemotherapy, cardiac progression was a leading cause of treatment failure in systemic AL amyloidosis with long-term survival (>1 year), even in the patients with hematologic CR. Continuation of chemotherapy or ASCT beyond hematologic response might be needed to achieve cardiac response and long-term survival in patients with AL amyloidosis who demonstrated cardiac progression. Further studies to elucidate the efficacy of chemotherapy beyond hematologic response are warranted.

Disclosures
No relevant conflicts of interest to declare.