Therapeutic Efficacy Analysis of 16 Patients with Primary Systemic Light Chain Amyloidosis Predominantly Exhibiting Advanced Cardiac Amyloidosis
Authors: Xue Hua , Wang Jing , Ye Shaojie , Guo Huimei , Zhao Songying , Liu Jia , Zhang Jiangbo , Xu Jianmei , Liu Yao 
Published: December 2024

Introduction

The primary systemic light chain amyloidosis(pAL) is a hematologic malignancy characterized by progressive organ dysfunction. Numerous studies have demonstrated that cardiac involvement significantly impacts patient prognosis, surpassing the effects of other organ involvement and serving as the leading cause of mortality. In order to achieve profound hematologic response in AL patients with cardiac involvement, several investigations have confirmed that rapid and deep hematologic response correlates closely with improved survival rates. In order to enhance our understanding of the treatment effectiveness for AL patients with cardiac involvement, the authors conducted a comprehensive analysis of 16 patients and provided an overview of their overall treatment approach. The majority of these 16 cases involved patients with advanced cardiac amyloidosis.

Methods

From May 2018 to August 2023, a total of 16 patients diagnosed with pAL cardiac involvement and treated in the hematology Department of the Affiliated Hospital of Hebei University were collected in this study.A retrospective analysis was conducted on 16 patients with cardiac involvement in pAL amyloidosis, who were divided into two treatment groups based on either bortezomib-containing regimens (VCD: bortezomib, cyclophosphamide, and dexamethasone; or VD: bortezomib and dexamethasone) or daratumumab-containing regimens (DVD: daratumumab plus VD; DVCD: daratumumab plus VCD; or DD: daratumumab and dexamethasone). The study assessed the hematologic response rate, cardiac response rate, survival outcomes, and adverse reactions in both patient cohorts.

Results

Among the 16 patients, 4 patients were at Mayo 2004 stage IIIa and 6 patients at Mayo 2004 stage IIIb. There was no significant difference in baseline characteristics between the two groups,but the proportion of patients with advanced cardiac amyloidosis was higher in the daratumumab group.The hematological response rate and cardiac organ response rate in the bortezomib-based treatment group were 33% and 11%, respectively. In contrast, the daratumumab-based treatment group exhibited a hematological response rate of 71% and a cardiac organ response rate of 57%. The median follow-up period was 11 months (2-40 months) for the bortezomib-based group, with a median progression-free survival (PFS) of 6 months. On the other hand, at a median follow-up of 12 months (2 to 25 months) in the daratumumab-based group, the median PFS was not reached. Survival curve analysis demonstrated a statistically significant PFS benefit in favor of the daratumumab-based group (P=0.022; P&lt;0.05). Although there was no statistically significant difference in overall survival (OS) between the two groups, it is worth noting that five patients from the bortezomib-based group switched to daratumumab-based treatment due to poor efficacy. This suggests that patients who transitioned to daratumumab based regimen after ineffective bortezomib based therapy still experienced some benefits. Furthermore, there were no significant differences.

Conclusions

The daratumumab-based regimen demonstrates efficacy in achieving haematological remission, cardiac response rate, and PFS benefit in patients with cardiac amyloidosis, without any significant difference in treatment tolerability compared to bortezomib-based therapy. Furthermore, transitioning to a daratumumab-based regimen may enhance therapeutic effectiveness and subsequently prolong overall survival.