Department of Internal Medicine V, Haematology and Medical Oncology, and.
Department of Medical Statistics, Informatics and Health Economics, Medical University of Innsbruck, Innsbruck, Austria.
Blood Adv. 2021 Mar 23;5(6):1746-1754. doi: 10.1182/bloodadvances.2020003193.
Monoclonal gammopathy of undetermined significance (MGUS), a premalignant condition, is associated with various chronic inflammatory rheumatic diseases (RDs) and is frequently observed as an incidental finding during routine work-up. The association of MGUS and chronic RDs is well established, but the impact of RDs on the risk of transformation into overt multiple myeloma (MM) has not been evaluated so far. MGUS patients diagnosed between January 2000 and August 2016 were identified and screened for concomitant RDs. RDs were grouped into antibody (Ab)-mediated RDs and non-Ab-mediated RDs (polymyalgia rheumatica, large-vessel giant cell arteritis, spondyloarthritis, and gout). Progression to MM was defined as a categorical (yes/no) or continuous time-dependent (time to progression) variable. Of 2935 MGUS patients, 255 (9%) had a concomitant RD. MGUS patients diagnosed with non-Ab-mediated RDs had a doubled risk of progression compared with those without a concomitant RD (hazard ratio, 2.1; 95% CI, 1.1-3.9; P = .02). These data translate into a 5-year risk of progression of 4% in MGUS patients without rheumatologic comorbidity, 10% in those with concomitant non-Ab-mediated RDS, and 2% in those with Ab-mediated RDs. By using the complex risk stratification model that includes myeloma protein (M-protein) concentration, immunoglobulin type, and level of free light chain ratio as variables, patients with non-Ab-mediated RDs (n = 57) had the highest risk for progression (hazard ratio, 6.8; 95% CI, 1.5-30.7; P = .01) compared with patients with Ab-mediated RDs (n = 77). Chronic inflammatory diseases have an impact on the risk of MGUS progressing into overt MM, with a doubled risk of transformation observed in patients with non-Ab-mediated RDs. Future research can elucidate whether comorbidities such as RDs should be included in currently applied prognostic MGUS scores.
意义未明的单克隆丙种球蛋白血症（MGUS）是一种癌前状态，与各种慢性炎症性风湿性疾病（RDs）相关，并且在常规检查中经常作为偶然发现。MGUS 与慢性 RDs 的关联已得到充分证实，但迄今为止，尚未评估 RDs 对转化为明显多发性骨髓瘤（MM）的风险的影响。本研究于 2000 年 1 月至 2016 年 8 月期间，对确诊为 MGUS 的患者进行识别和筛查，以明确其是否同时合并 RDs。RDs 分为抗体（Ab）介导的 RDs 和非 Ab 介导的 RDs（巨细胞动脉炎、大动脉炎、脊柱关节炎和痛风）。进展为 MM 定义为分类（是/否）或连续时间依赖（进展时间）变量。在 2935 例 MGUS 患者中，有 255 例（9%）同时合并 RDs。与无合并 RD 的患者相比，诊断为非 Ab 介导的 RDs 的 MGUS 患者的进展风险增加了一倍（风险比，2.1；95%置信区间，1.1-3.9；P =.02）。这意味着在无合并风湿学并发症的 MGUS 患者中，5 年进展风险为 4%，在伴有非 Ab 介导的 RDS 的患者中为 10%，在伴有 Ab 介导的 RDs 的患者中为 2%。通过使用包括骨髓瘤蛋白（M 蛋白）浓度、免疫球蛋白类型和游离轻链比值在内的复杂风险分层模型，非 Ab 介导的 RDs 患者（n = 57）的进展风险最高（风险比，6.8；95%置信区间，1.5-30.7；P =.01），而 Ab 介导的 RDs 患者（n = 77）的进展风险则较低。慢性炎症性疾病对 MGUS 进展为明显 MM 的风险有影响，非 Ab 介导的 RDs 患者的转化风险增加了一倍。未来的研究可以阐明是否应该将合并症（如 RDs）纳入当前应用的 MGUS 预后评分。
