意义未明的单克隆免疫球蛋白血症相关性肾损害（MGRS）患者的临床表现和长期生存结局：一项多中心回顾性研究。

Clinical Presentation and Long-Term Survival Outcomes of Patients With Monoclonal Gammopathy of Renal Significance (MGRS): A Multicenter Retrospective Study.

机构信息

IRCCS Azienda Ospedaliero-Universitaria di Bologna, Istituto di Ematologia "Seràgnoli", Bologna, Italy.

Dipartimento di Scienze Mediche e Chirurgiche, Università di Bologna, Bologna, Italy.

出版信息

Cancer Med. 2024 Nov;13(22):e70266. doi: 10.1002/cam4.70266.

DOI:10.1002/cam4.70266

PMID:39587728

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11588855/

Abstract

INTRODUCTION

MGRS are new rare clinical entities, whose recognition and optimal management is evolving.

METHODS

To implement real-life data, we retrospectively analysed a multicentre cohort of 60 patients with renal biopsy-proven MGRS receiving mainly novel treatments (between 2006 and 2021) in eight Italian centres. Based on renal biopsy, patients were divided into two subgroups: AL amyloidosis (70%, n = 42) and other-MGRS (30%, n = 18).

RESULTS

Baseline characteristics follow typical manifestations of MGRS disorders in terms of small clonal burden, laboratory and clinical features. More patients with AL amyloidosis had monotypic lambda light-chain disease, estimated glomerular filtration rate (eGFR) ≥ 60 mL/min and nephrotic proteinuria than other-MGRS group. The most widely used drug was bortezomib, and about one-third of patients underwent ASCT. Overall response rate was 86% with no differences in the two subgroups. However, high-quality hematologic responses ≥very good partial response (VGPR) were greater in AL amyloidosis than in other-MGRS group (67% vs 28%, p = 0.015). The depth of haematological response influenced renal response, obtained in 32 (59%) of evaluable patients, similarly in the subgroups. Indeed, 75% patients with ≥ VGPR (p = 0.049) and none with stable disease (p ≤ 0.001) obtained a renal response. No association between renal response and histotypes (p = 0.9) or type of first-line therapy (p = 0.3) was found. At a median follow-up of 54.4 months (IQR 24.8-102.8), median progression-free survival (PFS) was 100.1 months (95% CI 34.9-NR), and median overall survival not reached (95% CI 129.8-NR). No significant difference emerged between the two groups in terms of survival outcomes. Achieving ≥ VGPR was confirmed as the main independent predictor of prolonged PFS in the general population (HR = 0.29, p = 0.023) and AL amyloidosis group (HR 0.23; p = 0.023). Preserved renal function at diagnosis was predictive of improved PFS in the AL amyloidosis group (eGFR ≥ 60 mL/min: HR = 0.003; p = 0.018; eGFR 30-60 mL/min: HR = 0.04, p = 0.046).

CONCLUSION

Further research is warranted to develop standardised response criteria and treatment strategies to improve MGRS management.

摘要

简介

MGRS 是新的罕见临床实体，其识别和最佳管理正在不断发展。

方法

为了实施真实数据，我们回顾性分析了 60 名接受新型治疗（2006 年至 2021 年期间）的经肾活检证实的 MGRS 患者的多中心队列，这些患者来自意大利的 8 个中心。基于肾活检，患者被分为两个亚组：AL 淀粉样变性（70%，n=42）和其他-MGRS（30%，n=18）。

结果

基线特征符合 MGRS 疾病的典型表现，包括小克隆负担、实验室和临床特征。与其他-MGRS 组相比，AL 淀粉样变性患者更有可能患有单克隆 lambda 轻链疾病、估计肾小球滤过率（eGFR）≥60ml/min 和肾病蛋白尿。最广泛使用的药物是硼替佐米，约三分之一的患者接受了 ASCT。总缓解率为 86%，两个亚组之间无差异。然而，AL 淀粉样变性组的高质量血液学缓解率（≥非常好部分缓解（VGPR））高于其他-MGRS 组（67%比 28%，p=0.015）。血液学缓解的深度影响肾脏反应，在可评估的 32 名患者（59%）中获得了类似的反应，在亚组中也是如此。事实上，75%的≥VGPR 患者（p=0.049）和无稳定疾病患者（p≤0.001）获得了肾脏反应。肾脏反应与组织类型（p=0.9）或一线治疗类型（p=0.3）之间没有关联。在中位随访 54.4 个月（IQR 24.8-102.8）期间，中位无进展生存期（PFS）为 100.1 个月（95%CI 34.9-NR），总生存期未达到（95%CI 129.8-NR）。两组在生存结果方面无显著差异。在一般人群和 AL 淀粉样变性组中，达到≥VGPR 被确认为延长 PFS 的主要独立预测因素（HR=0.29，p=0.023）。在 AL 淀粉样变性组中，诊断时保留的肾功能可预测 PFS 改善（eGFR≥60ml/min：HR=0.003；p=0.018；eGFR 30-60ml/min：HR=0.04，p=0.046）。