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

当前位置： X-MOL 学术 › Amyloid › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Impact of cytogenetic abnormalities on treatment outcomes in patients with amyloid light-chain amyloidosis: subanalyses from the ANDROMEDA study
Amyloid ( IF 5.5 ) Pub Date : 2023-02-13 , DOI: 10.1080/13506129.2022.2164488
Shaji Kumar ₁ , Angela Dispenzieri ₁ , Divaya Bhutani ₂ , Morie Gertz ₁ , Ashutosh Wechalekar ₃ , Giovanni Palladini _{4,

5} , Raymond Comenzo ₆ , Rafael Fonseca ₇ , Arnaud Jaccard ₈ , Efstathios Kastritis ₉ , Stefan Schönland ₁₀ , Charles la Porte ₁₁ , Huiling Pei ₁₂ , NamPhuong Tran ₁₃ , Giampaolo Merlini _{4,

5}

Affiliation

Mayo Clinic Rochester, Rochester, MN, USA.
Department of Medicine, Division of Hematology/Oncology, Columbia University Medical Center, New York, NY, USA.
National Amyloidosis Centre, University College Hospital, London, UK.
Department of Molecular Medicine, University of Pavia, Pavia, Italy.
Amyloidosis Research and Treatment Center, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
Tufts Medical Center, John C Davis Myeloma and Amyloid Program, Boston, MA, USA.
Mayo Clinic, Phoenix, AZ, USA.
Centre Hospitalier Universitaire and Reference Center for AL Amyloidosis, Limoges, France.
Department of Clinical Therapeutics, National and Kapodistrian University of Athens, Athens, Greece.
Universitätsklinikum Heidelberg Medizinische Klinik V, Heidelberg, Germany.
Janssen Global Services, Breda, Netherlands.
Janssen Research & Development, LLC, Titusville, NJ, USA.
Janssen Research & Development, LLC, Los Angeles, CA, USA.

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.

中文翻译：

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：ANDROMEDA 研究的子分析

摘要

背景

细胞遗传学异常在淀粉样轻链 (AL) 淀粉样变性患者中很常见；有些与较差的结果有关。ANDROMEDA 的事后分析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 随机分配至达雷妥尤单抗、硼替佐米、环磷酰胺和地塞米松 (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

总体而言，321 名患者接受了细胞遗传学检测（D-VCd，n = 155；VCd，n = 166）；最常见的异常是 t(11;14) 和 amp1q21。中位随访时间为 20.3 个月，在所有细胞遗传学亚组中，D-VCd 的血液学完全缓解率均高于 VCd，并且在大多数亚组中，D-VCd 的器官缓解率在数值上更高。对于所有细胞遗传学亚组，主要器官恶化风险比的点估计-PFS 和-EFS 有利于D-VCd 而非VCd。在所有 ITT 和 t(11;14) 队列中，D-VCd 患者多于 VCd 患者，出现深度血液学反应（涉及减去未涉及的游离轻链 [FLC] <10 mg/L 或涉及的 FLC ≤20 mg/L）。