含达雷妥尤单抗方案治疗轻链型心脏淀粉样变性患者的早期经验。

Early experience with daratumumab-containing regimens in patients with light-chain cardiac amyloidosis.

作者信息

Morikawa Kei, Izumiya Yasuhiro, Takashio Seiji, Kawano Yawara, Oguni Tetsuya, Kuyama Naoto, Oike Fumi, Yamamoto Masahiro, Tabata Noriaki, Ishii Masanobu, Hanatani Shinsuke, Hoshiyama Tadashi, Kanazawa Hisanori, Matsuzawa Yasushi, Usuku Hiroki, Yamamoto Eiichiro, Ueda Mitsuharu, Tsujita Kenichi

机构信息

Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.

出版信息

J Cardiol. 2025 Jun;85(6):440-446. doi: 10.1016/j.jjcc.2024.11.003. Epub 2024 Dec 4.

DOI:10.1016/j.jjcc.2024.11.003

PMID:39577830

Abstract

BACKGROUND

Immunoglobulin light-chain (AL) amyloidosis is a lethal condition resulting from misfolded immunoglobulin ALs produced by clonal CD38-positive plasma cells. Treatment with daratumumab, an anti-human CD38 monoclonal antibody, led to higher frequencies of complete hematologic response and better clinical outcomes compared with conventional treatment. This study sought to evaluate the survival benefit of daratumumab-containing regimens in patients with AL cardiac amyloidosis.

METHODS AND RESULTS

We examined 65 consecutive patients with AL cardiac amyloidosis (mean age: 67.2 ± 10.4 years, male: 69 %) who underwent chemotherapy. We divided patients into a daratumumab group, which used daratumumab-containing regimens before second-line treatment (n = 32), and a conventional treatment group (n = 33). Compared with the conventional treatment group, the daratumumab group tended to be older, but there were no significant differences between groups in biomarkers and echocardiographic parameters. A total of 26 patients (40 %) died (median follow-up duration: 395 days). Kaplan-Meier survival analysis showed that the daratumumab group had significantly lower mortality compared with the conventional treatment group (p = 0.04; log-rank test). Cox hazard analysis revealed that use of daratumumab-containing regimens was associated with lower mortality after adjustment for the revised Mayo staging of AL amyloidosis (hazard ratio: 0.32; 95 % confidence interval: 0.12 to 0.85; p = 0.02).

CONCLUSION

Daratumumab-containing regimens may be associated with improved survival in patients with AL cardiac amyloidosis.

摘要

背景

免疫球蛋白轻链（AL）淀粉样变性是一种由克隆性CD38阳性浆细胞产生的错误折叠免疫球蛋白AL导致的致命疾病。与传统治疗相比，使用抗人CD38单克隆抗体达雷妥尤单抗进行治疗可使完全血液学缓解的频率更高，临床结局更好。本研究旨在评估含达雷妥尤单抗方案对AL心脏淀粉样变性患者的生存获益。

方法与结果

我们检查了65例接受化疗的连续性AL心脏淀粉样变性患者（平均年龄：67.2±10.4岁，男性：69%）。我们将患者分为达雷妥尤单抗组（n = 32），该组在二线治疗前使用含达雷妥尤单抗的方案，以及传统治疗组（n = 33）。与传统治疗组相比，达雷妥尤单抗组患者年龄往往更大，但两组在生物标志物和超声心动图参数方面无显著差异。共有26例患者（40%）死亡（中位随访时间：395天）。Kaplan-Meier生存分析显示，达雷妥尤单抗组的死亡率显著低于传统治疗组（p = 0.04；对数秩检验）。Cox风险分析显示，在对AL淀粉样变性的修订梅奥分期进行调整后，使用含达雷妥尤单抗的方案与较低的死亡率相关（风险比：0.32；95%置信区间：0.12至0.85；p = 0.02）。