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Graded Organ Response and Progression Criteria for Kidney Immunoglobulin Light Chain Amyloidosis
JAMA Oncology ( IF 22.5 ) Pub Date : 2024-08-01 , DOI: 10.1001/jamaoncol.2024.2629 Eli Muchtar 1 , Brendan Wisniowski 2 , Susan Geyer 3 , Giovanni Palladini 4, 5 , Paolo Milani 4, 5 , Giampaolo Merlini 4, 5 , Stefan Schönland 6 , Kaya Veelken 6 , Ute Hegenbart 6 , Nelson Leung 1 , Angela Dispenzieri 1 , Shaji K Kumar 1 , Efstathios Kastritis 7 , Meletios A Dimopoulos 7 , Michaela Liedtke 8 , Patricia Ulloa 8 , Vaishali Sanchorawala 9 , Raphael Szalat 9 , Katharine Dooley 3 , Heather Landau 10 , Erica Petrlik 10 , Suzanne Lentzsch 11 , Alexander Coltoff 11 , Joan Bladé 12 , M Teresa Cibeira 12 , Oliver Cohen 2 , Darren Foard 2 , Jullian Gillmore 2 , Helen Lachmann 2 , Ashutosh Wechalekar 2 , Morie A Gertz 1
JAMA Oncology ( IF 22.5 ) Pub Date : 2024-08-01 , DOI: 10.1001/jamaoncol.2024.2629 Eli Muchtar 1 , Brendan Wisniowski 2 , Susan Geyer 3 , Giovanni Palladini 4, 5 , Paolo Milani 4, 5 , Giampaolo Merlini 4, 5 , Stefan Schönland 6 , Kaya Veelken 6 , Ute Hegenbart 6 , Nelson Leung 1 , Angela Dispenzieri 1 , Shaji K Kumar 1 , Efstathios Kastritis 7 , Meletios A Dimopoulos 7 , Michaela Liedtke 8 , Patricia Ulloa 8 , Vaishali Sanchorawala 9 , Raphael Szalat 9 , Katharine Dooley 3 , Heather Landau 10 , Erica Petrlik 10 , Suzanne Lentzsch 11 , Alexander Coltoff 11 , Joan Bladé 12 , M Teresa Cibeira 12 , Oliver Cohen 2 , Darren Foard 2 , Jullian Gillmore 2 , Helen Lachmann 2 , Ashutosh Wechalekar 2 , Morie A Gertz 1
Affiliation
ImportanceKidney light chain (AL) amyloidosis is associated with a risk of progression to kidney replacement therapy (KRT) and death. Several studies have shown that a greater reduction in proteinuria following successful anticlonal therapy is associated with improved outcomes.ObjectiveTo validate graded kidney response criteria and their association with kidney and overall survival (OS).Design, Setting, and ParticipantsThis retrospective, multicenter cohort was conducted at 10 referral centers for amyloidosis from 2010 to 2015 and included patients with kidney AL amyloidosis that was evaluable for kidney response and who achieved at least hematologic partial response within 12 months of diagnosis. The median follow-up was 69 (54-88) months. Data analysis was conducted in 2023.ExposureFour kidney response categories based on the reduction in pretreatment 24-hour urine protein (24-hour UP) levels: complete response (kidCR, 24-hour UP ≤200 mg), very good partial response (kidVGPR, >60% reduction in 24-hour UP), partial response (kidPR, 31%-60% reduction), and no response (kidNR, ≤30% reduction). Kidney response was assessed at landmark points (6, 12, and 24 months) and best kidney response.Main Outcomes and MeasuresCumulative incidence of progression to KRT and OS.ResultsSeven-hundred and thirty-two patients (335 women [45.8%]) were included, with a median (IQR) age of 63 (55-69) years. The median (IQR) baseline 24-hour proteinuria and estimated glomerular filtration rate was 5.3 (2.8-8.5) g per 24 hours and 72 (48-92) mL/min/1.73m2 , respectively. In a competing-risk analysis, the 5-year cumulative incidence rates of progression to KRT decreased with deeper kidney responses as early as 6 months from therapy initiation (11%, 12%, 2.1%, and 0% for kidNR, kidPR, kidVGPR, and kidCR, respectively; P = .002) and were maintained at 12 months and 24 months and best kidney response. Patients able to achieve kidCR/kidVGPR by 24 months and at best response had significantly better OS compared with kidPR/kidNR. Kidney progression, defined as a 25% or greater decrease in estimated glomerular filtration rate, was associated with cumulative incidence of progression to KRT and OS.Conclusions and RelevanceThe results of this cohort study suggest that graded kidney response criteria offers clinically and prognostically meaningful information for treating patients with kidney AL amyloidosis. The response criteria potentially inform kidney survival based on the depth of reduction in 24-hour proteinuria levels and demonstrate an OS advantage for those able to achieve kidCR/kidVGPR compared with kidPR/kidNR. Taken together, achievement of at least kidVGPR by 12 months is needed to ultimately improve kidney and patient survival.
中文翻译:
肾免疫球蛋白轻链淀粉样变性的分级器官反应和进展标准
重要性肾轻链 (AL) 淀粉样变性与进展为肾脏替代疗法 (KRT) 和死亡的风险相关。几项研究表明,抗克隆治疗成功后蛋白尿的减少程度更高与结局改善相关。目的验证分级肾脏反应标准及其与肾脏和总生存期 (OS) 的相关性。设计、设置和参与者该回顾性多中心队列于 2010 年至 2015 年在 10 个淀粉样变性转诊中心进行,包括可评估肾脏反应且在诊断后 12 个月内至少达到血液学部分反应的肾 AL 淀粉样变性患者。中位随访时间为 69 (54-88) 个月。数据分析于 2023 年进行。暴露基于治疗前 24 小时尿蛋白 (24 小时 UP) 水平减少的四个肾脏反应类别:完全反应(kidCR,24 小时 UP ≤200 mg),非常好的部分反应(kidVGPR,>24 小时 UP 减少 60%)、部分缓解(kidPR,减少 31%-60%)和无反应(kidNR,减少 ≤30%)。在标志性点 (6 、 12 和 24 个月) 评估肾脏反应和最佳肾脏反应。主要结局和测量进展为 KRT 和 OS 的累积发生率。结果纳入 732 例患者 (335 名女性 [45.8%]),中位 (IQR) 年龄为 63 (55-69) 岁。中位 (IQR) 基线 24 小时蛋白尿和估计肾小球滤过率分别为 5.3 (2.8-8.5) g/24 小时和 72 (48-92) mL/min/1.73m2。在竞争风险分析中,早在治疗开始后 6 个月,随着肾脏反应的加深,进展为 KRT 的 5 年累积发生率降低 (11%, 12%, 2.kidNR、kidPR、kidVGPR 和 kidCR 分别为 1% 和 0%;P = .002),并维持在 12 个月和 24 个月且最佳肾脏反应。与 kidPR/kidNR 相比,能够在 24 个月时达到 kidCR/kidVGPR 且最佳反应的患者具有显着更好的 OS。肾脏进展,定义为估计肾小球滤过率降低 25% 或更多,与进展为 KRT 和 OS 的累积发生率相关。结论和相关性该队列研究的结果表明,分级肾反应标准为治疗肾 AL 淀粉样变性患者提供了具有临床和预后意义的信息。反应标准可能根据 24 小时蛋白尿水平降低的深度来告知肾脏生存率,并证明与 kidPR/kidNR 相比,能够达到 kidCR/kidVGPR 的患者具有 OS 优势。综上所述,需要在 12 个月前至少达到 kidVGPR 才能最终提高肾脏和患者的生存率。
更新日期:2024-08-01
中文翻译:
肾免疫球蛋白轻链淀粉样变性的分级器官反应和进展标准
重要性肾轻链 (AL) 淀粉样变性与进展为肾脏替代疗法 (KRT) 和死亡的风险相关。几项研究表明,抗克隆治疗成功后蛋白尿的减少程度更高与结局改善相关。目的验证分级肾脏反应标准及其与肾脏和总生存期 (OS) 的相关性。设计、设置和参与者该回顾性多中心队列于 2010 年至 2015 年在 10 个淀粉样变性转诊中心进行,包括可评估肾脏反应且在诊断后 12 个月内至少达到血液学部分反应的肾 AL 淀粉样变性患者。中位随访时间为 69 (54-88) 个月。数据分析于 2023 年进行。暴露基于治疗前 24 小时尿蛋白 (24 小时 UP) 水平减少的四个肾脏反应类别:完全反应(kidCR,24 小时 UP ≤200 mg),非常好的部分反应(kidVGPR,>24 小时 UP 减少 60%)、部分缓解(kidPR,减少 31%-60%)和无反应(kidNR,减少 ≤30%)。在标志性点 (6 、 12 和 24 个月) 评估肾脏反应和最佳肾脏反应。主要结局和测量进展为 KRT 和 OS 的累积发生率。结果纳入 732 例患者 (335 名女性 [45.8%]),中位 (IQR) 年龄为 63 (55-69) 岁。中位 (IQR) 基线 24 小时蛋白尿和估计肾小球滤过率分别为 5.3 (2.8-8.5) g/24 小时和 72 (48-92) mL/min/1.73m2。在竞争风险分析中,早在治疗开始后 6 个月,随着肾脏反应的加深,进展为 KRT 的 5 年累积发生率降低 (11%, 12%, 2.kidNR、kidPR、kidVGPR 和 kidCR 分别为 1% 和 0%;P = .002),并维持在 12 个月和 24 个月且最佳肾脏反应。与 kidPR/kidNR 相比,能够在 24 个月时达到 kidCR/kidVGPR 且最佳反应的患者具有显着更好的 OS。肾脏进展,定义为估计肾小球滤过率降低 25% 或更多,与进展为 KRT 和 OS 的累积发生率相关。结论和相关性该队列研究的结果表明,分级肾反应标准为治疗肾 AL 淀粉样变性患者提供了具有临床和预后意义的信息。反应标准可能根据 24 小时蛋白尿水平降低的深度来告知肾脏生存率,并证明与 kidPR/kidNR 相比,能够达到 kidCR/kidVGPR 的患者具有 OS 优势。综上所述,需要在 12 个月前至少达到 kidVGPR 才能最终提高肾脏和患者的生存率。