Clinica Universidad de Navarra, Centro de Investigacion Medica Aplicada (CIMA), Instituto de Investigacion Sanitaria de Navarra (IDISNA), CCUN, CIBER-ONC numbers CB16/12/00369, CB16/12/00489, Pamplona, Spain.
Department of Hematooncology, University Hospital Ostrava and University of Ostrava, Ostrava, Czech Republic.
Clin Cancer Res. 2022 Nov 1;28(21):4771-4781. doi: 10.1158/1078-0432.CCR-22-1594.
Early intervention in smoldering multiple myeloma (SMM) requires optimal risk stratification to avoid under- and overtreatment. We hypothesized that replacing bone marrow (BM) plasma cells (PC) for circulating tumor cells (CTC), and adding immune biomarkers in peripheral blood (PB) for the identification of patients at risk of progression due to lost immune surveillance, could improve the International Myeloma Working Group 20/2/20 model.
We report the outcomes of 150 patients with SMM enrolled in the iMMunocell study, in which serial assessment of tumor and immune cells in PB was performed every 6 months for a period of 3 years since enrollment.
Patients with >0.015% versus ≤0.015% CTCs at baseline had a median time-to-progression of 17 months versus not reached (HR, 4.9; P < 0.001). Presence of >20% BM PCs had no prognostic value in a multivariate analysis that included serum free light-chain ratio >20, >2 g/dL M-protein, and >0.015% CTCs. The 20/2/20 and 20/2/0.015 models yielded similar risk stratification (C-index of 0.76 and 0.78). The combination of the 20/2/0.015 model with an immune risk score based on the percentages of SLAN+ and SLAN- nonclassical monocytes, CD69+HLADR+ cytotoxic NK cells, and CD4+CXCR3+ stem central memory T cells, allowed patient' stratification into low, intermediate-low, intermediate-high, and high-risk disease with 0%, 20%, 39%, and 73% rates of progression at 2 years.
This study showed that CTCs outperform BM PCs for assessing tumor burden. Additional analysis in larger series are needed to define a consensus cutoff of CTCs for minimally invasive stratification of SMM.
冒烟型多发性骨髓瘤（SMM）的早期干预需要进行最佳风险分层，以避免治疗不足和过度治疗。我们假设，用外周血（PB）中的循环肿瘤细胞（CTC）替代骨髓（BM）中的浆细胞（PC），并添加免疫生物标志物，以识别因免疫监视丧失而有进展风险的患者，可改进国际骨髓瘤工作组 20/2/20 模型。
我们报告了在 iMMunocell 研究中纳入的 150 例 SMM 患者的结果，该研究在纳入后 3 年内，每 6 个月对 PB 中的肿瘤和免疫细胞进行连续评估。
基线时 CTCs＞0.015%与 CTCs≤0.015%的患者，中位无进展时间分别为 17 个月和未达到（HR，4.9；P＜0.001）。在包括血清游离轻链比＞20、＞2 g/dL M 蛋白和 CTCs＞0.015%的多变量分析中，BM 中＞20%PCs 无预后价值。20/2/20 和 20/2/0.015 模型的风险分层相似（C 指数分别为 0.76 和 0.78）。20/2/0.015 模型与基于 SLAN+和 SLAN-非经典单核细胞、CD69+HLADR+细胞毒性 NK 细胞和 CD4+CXCR3+干细胞中央记忆 T 细胞百分比的免疫风险评分相结合，可将患者分为低危、中低危、中高危和高危疾病，在 2 年内，进展率分别为 0%、20%、39%和 73%。
本研究表明，CTC 比 BM PCs 更能评估肿瘤负担。需要在更大的系列中进行进一步分析，以确定 CTC 用于 SMM 微创分层的共识界值。
