Department of Hematology, Japanese Red Cross Medical Center, Tokyo, Japan.
Division of Medicine, Faculty of Medical Sciences, University College London and the Royal Free London NHS Foundation Trust, London, UK.
Ann Hematol. 2023 Apr;102(4):863-876. doi: 10.1007/s00277-023-05090-z. Epub 2023 Mar 2.
Subcutaneous daratumumab plus bortezomib/cyclophosphamide/dexamethasone (VCd; D-VCd) improved outcomes versus VCd for patients with newly diagnosed immunoglobulin light-chain (AL) amyloidosis in the phase 3 ANDROMEDA study. We report a subgroup analysis of Asian patients (Japan; Korea; China) from ANDROMEDA. Among 388 randomized patients, 60 were Asian (D-VCd, n = 29; VCd, n = 31). At a median follow-up of 11.4 months, the overall hematologic complete response rate was higher for D-VCd versus VCd (58.6% vs. 9.7%; odds ratio, 13.2; 95% confidence interval [CI], 3.3-53.7; P < 0.0001). Six-month cardiac and renal response rates were higher with D-VCd versus VCd (cardiac, 46.7% vs. 4.8%; P = 0.0036; renal, 57.1% vs. 37.5%; P = 0.4684). Major organ deterioration progression-free survival (MOD-PFS) and major organ deterioration event-free survival (MOD-EFS) were improved with D-VCd versus VCd (MOD-PFS: hazard ratio [HR], 0.21; 95% CI, 0.06-0.75; P = 0.0079; MOD-EFS: HR, 0.16; 95% CI, 0.05-0.54; P = 0.0007). Twelve deaths occurred (D-VCd, n = 3; VCd, n = 9). Twenty-two patients had baseline serologies indicating prior hepatitis B virus (HBV) exposure; no patient experienced HBV reactivation. Although grade 3/4 cytopenia rates were higher than in the global safety population, the safety profile of D-VCd in Asian patients was generally consistent with the global study population, regardless of body weight. These results support D-VCd use in Asian patients with newly diagnosed AL amyloidosis. ClinicalTrials.gov Identifier: NCT03201965.
在 3 期 ANDROMEDA 研究中,皮下注射达雷妥尤单抗联合硼替佐米/环磷酰胺/地塞米松(VCd;D-VCd)治疗新诊断的免疫球蛋白轻链(AL)淀粉样变性患者的结局优于 VCd。我们报告了 ANDROMEDA 亚洲患者(日本;韩国;中国)的亚组分析。在 388 名随机患者中,有 60 名是亚洲人(D-VCd,n=29;Vc,n=31)。在中位随访 11.4 个月时,D-VCd 组的总体血液学完全缓解率高于 VCd 组(58.6%比 9.7%;比值比,13.2;95%置信区间[CI],3.3-53.7;P<0.0001)。D-VCd 组的 6 个月心脏和肾脏缓解率高于 VCd 组(心脏,46.7%比 4.8%;P=0.0036;肾脏,57.1%比 37.5%;P=0.4684)。D-VCd 组的主要器官恶化无进展生存期(MOD-PFS)和主要器官恶化无事件生存期(MOD-EFS)均优于 VCd 组(MOD-PFS:风险比[HR],0.21;95%CI,0.06-0.75;P=0.0079;MOD-EFS:HR,0.16;95%CI,0.05-0.54;P=0.0007)。发生 12 例死亡(D-VCd,n=3;Vc,n=9)。22 名患者基线血清学提示既往乙型肝炎病毒(HBV)暴露;无患者发生 HBV 再激活。尽管 3/4 级细胞减少症发生率高于全球安全性人群,但 D-VCd 在亚洲患者中的安全性概况与全球研究人群大致一致,与体重无关。这些结果支持 D-VCd 用于新诊断的 AL 淀粉样变性的亚洲患者。临床试验.gov 标识符:NCT03201965。