Impact of cytogenetic abnormalities on treatment outcomes in patients with amyloid light-chain amyloidosis: subanalyses from the ANDROMEDA study.

IF 5.2 2区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Shaji Kumar, Angela Dispenzieri, Divaya Bhutani, Morie Gertz, Ashutosh Wechalekar, Giovanni Palladini, Raymond Comenzo, Rafael Fonseca, Arnaud Jaccard, Efstathios Kastritis, Stefan Schönland, Charles la Porte, Huiling Pei, NamPhuong Tran, Giampaolo Merlini
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引用次数: 4

Abstract

Background: Cytogenetic abnormalities are common in patients with amyloid light-chain (AL) amyloidosis; some are associated with poorer outcomes. This post hoc analysis of ANDROMEDA evaluated the impact of certain cytogenetic abnormalities on outcomes in this patient population.

Methods: Patients with newly diagnosed AL amyloidosis were randomised 1:1 to daratumumab, bortezomib, cyclophosphamide, and dexamethasone (D-VCd) or VCd. Outcomes were evaluated in the intent-to-treat (ITT) population and in patients with t(11;14), amp1q21, del13q14, and del17p13.

Results: Overall, 321 patients had cytogenetic testing (D-VCd, n = 155; VCd, n = 166); most common abnormalities were t(11;14) and amp1q21. At a median follow-up of 20.3 months, haematologic complete response rates were higher with D-VCd vs VCd across all cytogenetic subgroups and organ response rates were numerically higher with D-VCd vs VCd across most subgroups. Point estimates for hazard ratio of major organ deterioration-PFS and -EFS favoured D-VCd over VCd for all cytogenetic subgroups. Deep haematologic responses (involved minus uninvolved free light chains [FLC] <10 mg/L or involved FLC ≤20 mg/L) were seen in more patients with D-VCd than VCd in all ITT and t(11;14) cohorts.

Conclusions: These results support the use of D-VCd as standard of care in patients with newly diagnosed AL amyloidosis regardless of cytogenetic abnormalities.

细胞遗传学异常对淀粉样蛋白轻链淀粉样变性患者治疗结果的影响:来自ANDROMEDA研究的亚分析
背景:细胞遗传学异常在淀粉样蛋白轻链(AL)淀粉样变性患者中很常见;有些与较差的结果有关。这个事后分析的ANDROMEDA评估了某些细胞遗传学异常对该患者群体结果的影响。方法:新诊断的AL淀粉样变性患者按1:1随机分配至达拉单抗、硼替佐米、环磷酰胺和地塞米松组(D-VCd)或VCd组。在意向治疗(ITT)人群和t(11;14)、amp1q21、del13q14和del17p13患者中评估结果。结果:321例患者进行了细胞遗传学检测(D-VCd, n = 155;VCd, n = 166);最常见的异常是t(11;14)和amp1q21。在20.3个月的中位随访中,在所有细胞遗传学亚组中,D-VCd与VCd的血液学完全缓解率更高,在大多数亚组中,D-VCd与VCd的器官反应率在数值上更高。主要器官恶化的风险比- pfs和-EFS的点估计在所有细胞遗传学亚组中都倾向于D-VCd而不是VCd。结论:这些结果支持将D-VCd作为新诊断的AL淀粉样变性患者的标准治疗,无论细胞遗传学异常如何。
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来源期刊
Amyloid-Journal of Protein Folding Disorders
Amyloid-Journal of Protein Folding Disorders 生物-生化与分子生物学
CiteScore
10.60
自引率
10.90%
发文量
48
审稿时长
6-12 weeks
期刊介绍: Amyloid: the Journal of Protein Folding Disorders is dedicated to the study of all aspects of the protein groups and associated disorders that are classified as the amyloidoses as well as other disorders associated with abnormal protein folding. The journals major focus points are: etiology, pathogenesis, histopathology, chemical structure, nature of fibrillogenesis; whilst also publishing papers on the basic and chemical genetic aspects of many of these disorders. Amyloid is recognised as one of the leading publications on amyloid protein classifications and the associated disorders, as well as clinical studies on all aspects of amyloid related neurodegenerative diseases and major clinical studies on inherited amyloidosis, especially those related to transthyretin. The Journal also publishes book reviews, meeting reports, editorials, thesis abstracts, review articles and symposia in the various areas listed above.
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