Landgren Ola, Hofmann Jonathan N, McShane Charlene M, Santo Loredana, Hultcrantz Malin, Korde Neha, Mailankody Sham, Kazandjian Dickran, Murata Kazunori, Thoren Katie, Ramanathan Lakshmi, Dogan Ahmet, Rustad Even, Lu Sydney X, Akhlaghi Theresia, Kristinsson Sigurdur Y, Björkholm Magnus, Devlin Sean, Purdue Mark P, Pfeiffer Ruth M, Turesson Ingemar
Myeloma Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.
Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland.
JAMA Oncol. 2019 Sep 1;5(9):1293-1301. doi: 10.1001/jamaoncol.2019.1568.
Multiple myeloma is consistently preceded by monoclonal gammopathy of undetermined significance (MGUS). Risk models that estimate the risk of progression from MGUS to multiple myeloma use data from a single time point, usually the initial workup.
To longitudinally investigate the alterations of serum immune markers with stable vs progressive MGUS.
DESIGN, SETTING, AND PARTICIPANTS: This prospective cross-sectional cohort study included 77 469 adult participants aged 55 to 74 years in the screening arm of the National Cancer Institute Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial who had a diagnosis of progressing MGUS (n = 187) or stable MGUS (n = 498), including light-chain subtype, from November 1993, through December 2011. For each participant, all available serially stored prediagnostic serum samples (N = 3266) were obtained. Data analysis was performed from April 2018, to December 2018.
Serum protein and monoclonal immunoglobulin levels, serum free light chains, and serum light chains within each immunoglobulin class were measured.
Of 685 individuals included in the study, 461 (67.3%) were men; the mean (SD) age was 69.1 (5.6) years. In cross-sectional modeling, risk factors associated with progressive MGUS were IgA isotype (adjusted odds ratio [OR], 1.80; 95% CI, 1.03-3.13; P = .04), 15 g/L or more monoclonal spike (adjusted OR, 23.5; 95% CI, 8.9-61.9; P < .001), skewed (<0.1 or >10) serum free light chains ratio (adjusted OR, 46.4; 95% CI, 18.4-117.0; P < .001), and severe immunoparesis (≥2 suppressed uninvolved immunoglobulins) (adjusted OR, 19.1; 95% Cl, 7.5-48.3; P < .001). Risk factors associated with progressive light-chain MGUS were skewed serum free light chains ratio (adjusted OR, 44.0; 95% CI, 14.2-136.3; P < .001) and severe immunoparesis (adjusted OR, 48.6; 95% CI, 9.5-248.2; P < .001). In longitudinal analysis of participants with serial samples prior to progression, 23 of 43 participants (53%) had high-risk MGUS before progression; 16 of these 23 (70%) experienced conversion from low-risk or intermediate-risk MGUS within 5 years. Similar results were found for light-chain MGUS.
The findings of evolving risk patterns support annual blood testing and risk assessment for patients with MGUS or light-chain MGUS.
多发性骨髓瘤之前始终存在意义未明的单克隆丙种球蛋白病（MGUS）。估计MGUS进展为多发性骨髓瘤风险的模型使用来自单个时间点的数据，通常是初始检查数据。
纵向研究稳定型与进展型MGUS患者血清免疫标志物的变化。
设计、设置和参与者：这项前瞻性横断面队列研究纳入了美国国立癌症研究所前列腺、肺、结直肠癌和卵巢癌筛查试验筛查组中77469名年龄在55至74岁的成年参与者，他们在1993年11月至2011年12月期间被诊断为进展型MGUS（n = 187）或稳定型MGUS（n = 498），包括轻链亚型。为每位参与者获取了所有可用的系列储存的诊断前血清样本（N = 3266）。数据分析于2018年4月至2018年12月进行。
测量血清蛋白和单克隆免疫球蛋白水平、血清游离轻链以及各免疫球蛋白类别中的血清轻链。
纳入研究的685名个体中，461名（67.3%）为男性；平均（标准差）年龄为69.1（5.6）岁。在横断面模型中，与进展型MGUS相关的危险因素为IgA亚型（调整优势比[OR]，1.80；95%可信区间[CI]，1.03 - 3.13；P = 0.04）、单克隆峰≥15 g/L（调整OR，23.5；95% CI，8.9 - 61.9；P < 0.001）、血清游离轻链比值偏态（<0.1或>10）（调整OR，46.4；95% CI，18.4 - 117.0；P < 0.001）以及严重免疫球蛋白减少（≥2种未受累免疫球蛋白受抑制）（调整OR，19.1；95% CI，7.5 - 48.3；P < 0.001）。与进展型轻链MGUS相关的危险因素为血清游离轻链比值偏态（调整OR，44.0；95% CI，14.2 - 136.3；P < 0.001）和严重免疫球蛋白减少（调整OR，48.6；9
