Clínica Universidad de Navarra, Centro de Investigación Médica Aplicada, Universidad de Navarra, CCUN, IDISNA, CIBERONC, Pamplona, Spain.
Hospital Universitario de Salamanca (HUSAL), IBSAL, IBMCC (USAL-CSIC), CIBERONC, Salamanca, Spain.
J Clin Oncol. 2023 Jun 1;41(16):3019-3031. doi: 10.1200/JCO.22.01916. Epub 2023 Mar 17.
The existence of patients with multiple myeloma (MM) and light-chain (AL) amyloidosis who present with a monoclonal gammopathy of undetermined significance (MGUS)-like phenotype has been hypothesized, but methods to identify this subgroup are not standardized and its clinical significance is not properly validated.
An algorithm to identify patients having MGUS-like phenotype was developed on the basis of the percentages of total bone marrow (BM) plasma cells (PC) and of clonal PC within the BM PC compartment, determined at diagnosis using flow cytometry in 548 patients with MGUS and 2,011 patients with active MM. The clinical significance of the algorithm was tested and validated in 488 patients with smoldering MM, 3,870 patients with active MM and 211 patients with AL amyloidosis.
Patients with smoldering MM with MGUS-like phenotype showed significantly lower rates of disease progression (4.5% and 0% at 2 years in two independent series). There were no statistically significant differences in time to progression between treatment versus observation in these patients. In active newly diagnosed MM, MGUS-like phenotype retained independent prognostic value in multivariate analyses of progression-free survival (PFS; hazard ratio [HR], 0.49; = .001) and overall survival (OS; HR, 0.56; = .039), together with International Staging System, lactate dehydrogenase, cytogenetic risk, transplant eligibility, and complete remission status. Transplant-eligible patients with active MM with MGUS-like phenotype showed PFS and OS rates at 5 years of 79% and 96%, respectively. In this subgroup, there were no differences in PFS and OS according to complete remission and measurable residual disease status. Application of the algorithm in two independent series of patients with AL predicted for different survival.
We developed an open-access algorithm for the identification of MGUS-like patients with distinct clinical outcomes. This phenotypic classification could become part of the diagnostic workup of MM and AL amyloidosis.
多发性骨髓瘤（MM）和轻链（AL）淀粉样变性患者存在类似于意义未明的单克隆丙种球蛋白血症（MGUS）的表型，这一假说已经提出，但识别这种亚组的方法尚未标准化，其临床意义也未得到充分验证。
我们基于流式细胞术在 548 例 MGUS 患者和 2011 例活动性 MM 患者中诊断时骨髓浆细胞（PC）和骨髓 PC 池内克隆性 PC 的百分比，开发了一种识别具有 MGUS 样表型患者的算法。该算法的临床意义在 488 例冒烟型 MM、3870 例活动性 MM 和 211 例 AL 淀粉样变性患者中进行了测试和验证。
具有 MGUS 样表型的冒烟型 MM 患者的疾病进展率明显较低（两个独立系列中，2 年时分别为 4.5%和 0%）。在这些患者中，治疗与观察之间的进展时间无统计学差异。在新发活动性 MM 中，MGUS 样表型在无进展生存（PFS）和总生存（OS）的多变量分析中保留了独立的预后价值（PFS：危险比 [HR]，0.49；P=0.001），与国际分期系统、乳酸脱氢酶、细胞遗传学风险、移植资格和完全缓解状态一起。具有 MGUS 样表型的可移植活动性 MM 患者的 5 年 PFS 和 OS 率分别为 79%和 96%。在这一亚组中，根据完全缓解和可测量残留疾病状态，PFS 和 OS 无差异。该算法在两个独立的 AL 患者系列中的应用预测了不同的生存。
我们开发了一种用于识别具有不同临床结局的 MGUS 样患者的开放获取算法。这种表型分类可能成为 MM 和 AL 淀粉样变性诊断的一部分。
