Department of Medicine, Stony Brook University School of Medicine, Stony Brook, NY.
Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY; and.
Blood Adv. 2018 Jun 26;2(12):1470-1479. doi: 10.1182/bloodadvances.2018016998.
We investigated the predictive role for serum free light chain ratio (FLCr) ≥100, bone marrow plasma cell (BMPC) ≥60%, and evolving biomarkers through group-based trajectory modeling (GBTM) as high-risk defining events in 273 smoldering multiple myeloma (SMM) patients with a median follow-up of 74 months. FLCr ≥100 was confirmed as a marker for high-risk progression with a median time to progression (TTP) of 40 months with a 44% risk of progression of disease (PD) at 2 years; however, 44% of FLCr ≥100 also did not progress during follow-up. For patients with BMPC ≥60% by core biopsy, the median TTP was 31 months with a 2-year PD of 41%. GBTM established high-risk trajectories for evolving hemoglobin (eHb; characterized as a 1.57 g/dL decrease in hemoglobin), evolving m-protein (eMP; 64% increase in m-protein), and evolving differences in FLC (edFLC; 169% increase in dFLC) within 1 year of diagnosis associated with a decreased median TTP and an increased 2 year rate of PD. Of all the variables examined, we identify a model where immunoparesis, eHb, eMP, and edFLC were significant predictors for ultra-high-risk progression with a median TTP of only 13 months with 3 or more variables present. Our results not only confirm a more modest 2 year PD associated with FLCr ≥100 and BMPC ≥60 but also suggest that eHb, eMP, and edFLC may help identify an ultra-high-risk SMM group.
我们通过基于群组的轨迹建模（GBTM）研究了血清游离轻链比（FLCr）≥100、骨髓浆细胞（BMPC）≥60%以及不断发展的生物标志物在 273 例冒烟型多发性骨髓瘤（SMM）患者中的预测作用，这些患者的中位随访时间为 74 个月。FLCr≥100 被确认为高风险进展的标志物，中位进展时间（TTP）为 40 个月，2 年内疾病进展（PD）的风险为 44%；然而，44%的 FLCr≥100 在随访期间也没有进展。对于核心活检中 BMPC≥60%的患者，中位 TTP 为 31 个月，2 年内 PD 发生率为 41%。GBTM 确定了高风险轨迹，用于在诊断后 1 年内发生的血红蛋白变化（eHb；血红蛋白下降 1.57g/dL）、M 蛋白变化（eMP；M 蛋白增加 64%）和游离轻链变化（edFLC；dFLC 增加 169%），这与中位 TTP 缩短和 2 年内 PD 发生率增加有关。在所有检查的变量中，我们确定了一种模型，其中免疫缺陷、eHb、eMP 和 edFLC 是超高风险进展的显著预测因子，中位 TTP 仅为 13 个月，同时存在 3 个或更多变量。我们的研究结果不仅证实了与 FLCr≥100 和 BMPC≥60%相关的更为适度的 2 年 PD，而且还表明 eHb、eMP 和 edFLC 可能有助于识别超高风险的 SMM 患者群体。
