建立一个多变量模型预测意义未明的单克隆丙种球蛋白血症患者骨髓活检的需求：一项嵌套在临床试验中的队列研究。

Development of a Multivariable Model to Predict the Need for Bone Marrow Sampling in Persons With Monoclonal Gammopathy of Undetermined Significance : A Cohort Study Nested in a Clinical Trial.

机构信息

Landspítali-The National University Hospital of Iceland and Faculty of Medicine, University of Iceland, Reykjavík, Iceland (E.E., S.R., P.T.O., B.A.A., R.P., O.S.I., S.Y.K.).

Faculty of Medicine, University of Iceland, Reykjavík, Iceland, and Department of Hematology, Rigshospitalet, Copenhagen, Denmark (S.T.).

出版信息

Ann Intern Med. 2024 Apr;177(4):449-457. doi: 10.7326/M23-2540. Epub 2024 Apr 2.

DOI:10.7326/M23-2540

PMID:38560901

Abstract

BACKGROUND

Monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM) are asymptomatic precursor conditions to multiple myeloma and related disorders. Smoldering multiple myeloma is distinguished from MGUS by 10% or greater bone marrow plasma cells (BMPC) on sampling, has a higher risk for progression, and requires specialist management.

OBJECTIVE

To develop a multivariable prediction model that predicts the probability that a person with presumed MGUS has 10% or greater BMPC (SMM or worse by bone marrow criteria) to inform the decision to obtain a bone marrow sample and compare its performance to the Mayo Clinic risk stratification model.

DESIGN

iStopMM (Iceland Screens, Treats or Prevents Multiple Myeloma), a prospective population-based screening study of MGUS. (ClinicalTrials.gov: NCT03327597).

SETTING

Icelandic population of adults aged 40 years or older.

PATIENTS

1043 persons with IgG, IgA, light-chain, and biclonal MGUS detected by screening and an interpretable bone marrow sample.

MEASUREMENTS

Monoclonal gammopathy of undetermined significance isotype; monoclonal protein concentration; free light-chain ratio; and total IgG, IgM, and IgA concentrations were used as predictors. Bone marrow plasma cells were categorized as 0% to 4%, 5% to 9%, 10% to 14%, or 15% or greater.

RESULTS

The c-statistic for SMM or worse was 0.85 (95% CI, 0.82 to 0.88), and calibration was excellent (intercept, -0.07; slope, 0.95). At a threshold of 10% predicted risk for SMM or worse, sensitivity was 86%, specificity was 67%, positive predictive value was 32%, and negative predictive value was 96%. Compared with the Mayo Clinic model, the net benefit for the decision to refer for sampling was between 0.13 and 0.30 higher over a range of plausible low-risk thresholds.

LIMITATION

The prediction model will require external validation.

CONCLUSION

This accurate prediction model for SMM or worse was developed in a population-based cohort of persons with presumed MGUS and may be used to defer bone marrow sampling and referral to hematology.

PRIMARY FUNDING SOURCE

International Myeloma Foundation and the European Research Council.

摘要

背景

意义未明的单克隆丙种球蛋白血症（MGUS）和冒烟型多发性骨髓瘤（SMM）是多发性骨髓瘤和相关疾病的无症状前体状态。冒烟型多发性骨髓瘤与 MGUS 的区别在于骨髓浆细胞（BMPC）占比 10%或以上（通过骨髓取样），进展风险更高，需要专科管理。

目的

开发一个多变量预测模型，以预测疑似 MGUS 患者骨髓中 BMPC 占比 10%或以上（骨髓标准为 SMM 或更差）的概率，以便决定是否进行骨髓取样，并将其性能与 Mayo 临床风险分层模型进行比较。

设计

iStopMM（冰岛筛查、治疗或预防多发性骨髓瘤）是一项针对 MGUS 的前瞻性基于人群的筛查研究。（ClinicalTrials.gov：NCT03327597）。

地点

冰岛 40 岁及以上成年人的人群。

患者

1043 名通过筛查发现的 IgG、IgA、轻链和双克隆 MGUS 患者，且其骨髓样本可解读。

测量方法

MGUS 同型、单克隆蛋白浓度、游离轻链比以及总 IgG、IgM 和 IgA 浓度被用作预测指标。骨髓浆细胞分为 0%至 4%、5%至 9%、10%至 14%或 15%或以上。

结果

SMM 或更差的 c 统计量为 0.85（95%CI，0.82 至 0.88），校准效果极佳（截距，-0.07；斜率，0.95）。在预测 SMM 或更差的风险阈值为 10%时，敏感性为 86%，特异性为 67%，阳性预测值为 32%，阴性预测值为 96%。与 Mayo 临床模型相比，在一系列低风险阈值范围内，决策是否进行取样的净获益增加了 0.13 至 0.30。