Efficacy and Safety of Anselamimab in Immunoglobulin Light Chain Amyloidosis: Results From the Randomized CARES Trials.

Anselamimab, a monoclonal antibody, selectively binds to amyloid fibrils, accelerating their clearance.

Anselamimab是一种单克隆抗体，它选择性地与淀粉样纤维结合，加速它们的清除。

Methods

Newly diagnosed patients with European modification of Mayo 2004 stage IIIa or IIIb AL amyloidosis were randomly assigned to receive anselamimab or placebo with cyclophosphamide, bortezomib, and dexamethasone (with or without daratumumab).

新诊断的欧洲版Mayo 2004 IIIa或IIIb期AL淀粉样变性患者被随机分配接受anselamimab或安慰剂，联合环磷酰胺、硼替佐米和地塞米松（可选加达雷妥尤单抗）。

The primary end point was a hierarchical composite of time to all-cause mortality (ACM) and frequency of cardiovascular hospitalizations (CVHs), analyzed using the Finkelstein-Schoenfeld test and win ratio estimation.

主要终点是一个分层复合终点，包括全因死亡时间（ACM）和心血管住院频率（CVHs），使用Finkelstein-Schoenfeld检验和胜率估计进行分析。

Results

Among 406 randomly assigned patients, the primary end point win ratio for anselamimab versus placebo was 1.11 (95% CI, 0.83, 1.50; P = .332) and the hazard ratio(HR) for ACM was 0.80 (95% CI, 0.57, 1.13; P = .290).

在406名随机分配的患者中，anselamimab与安慰剂的首要终点胜率比为1.11（95%置信区间，0.83，1.50；P = .332），全因死亡（ACM）的风险比为0.80（95%置信区间，0.57，1.13；P = .290）。

CVH rates in the anselamimab and placebo groups were 0.59 (95% CI, 0.42, 0.83) and 0.89 (95% CI, 0.55, 1.43), respectively (P = .145).

anselamimab组和安慰剂组的CVH率分别为0.59（95%置信区间，0.42，0.83）和0.89（95%置信区间，0.55，1.43）（P = .145）。

Among patients with kappa isotype (n = 72), the win ratio was 2.06 (95% CI, 0.98, 4.31; P = .100) and anselamimab reduced ACM by 62% versus placebo (HR, 0.38; 95% CI, 0.17 to 0.86; nominal P = .012), and CVH by 71% (IRR, 0.29; 95% CI, 0.10 to 0.87; nominal P = .028) with improvements in Kansas City Cardiomyopathy Questionnaire-Overall Score.

在具有kappa同种型的患者(n = 72)中，胜利比率是2.06 (95% 置信区间, 0.98, 4.31; P = .100)，而anselamimab与安慰剂相比，将全因死亡率(ACM)降低了62% (HR, 0.38; 95% 置信区间, 0.17至0.86; 名义P = .012)，将心血管死亡率(CVH)降低了71% (IRR, 0.29; 95% 置信区间, 0.10至0.87; 名义P = .028)，并改善了堪萨斯城心肌病问卷总体评分。

There was no clinical benefit observed in the lambda population.

在lambda同种型人群中未观察到临床益处。

Anselamimab was generally well-tolerated; safety data were comparable between treatment arms overall.

Anselamimab通常耐受性良好；总体上，治疗组之间的安全性数据是可比的。

Conclusions

Treatment with anselamimab, an antifibril antibody used alongside antiplasma cell dyscrasia therapy, while not meeting the primary end point in the overall population, significantly improved ACM and CVH in patients with kappa AL, potentially offering a new therapeutic option for this isotype.

在与抗浆细胞病治疗联合使用时，尽管在整体人群中未达到主要终点，但anselamimab（一种抗纤维蛋白抗体）显著改善了具有kappa轻链型淀粉样变性患者的ACM和CVH，可能为这种同型型提供了一种新的治疗选择。