Rare Tumors and Melanoma Unit, IRCCS Istituto Tumori "Giovanni Paolo II", Viale O. Flacco, 6570124, Bari, Italy.
Department of Biomedical Sciences and Human Oncology, University of Bari, Bari, Italy.
J Transl Med. 2022 Apr 5;20(1):159. doi: 10.1186/s12967-022-03359-x.
To evaluate the capability of basal and one-month differed white blood cells (WBC), neutrophil, lymphocyte and platelet values and their ratios (neutrophils-to-lymphocytes ratio, NLR, and platelets-to-lymphocytes ratio, PLR) in predicting the response to immune checkpoint inhibitors (ICI) in metastatic melanoma (MM).
We performed a retrospective study of 272 BRAF wild-type MM patients treated with first line ICI. Bivariable analysis was used to correlate patient/tumor characteristics with clinical outcomes. Variations between time 1 and time 0 (Δ) of blood parameters were also calculated and dichotomized using cut-off values assessed by ROC curve.
At baseline, higher neutrophils and NLR negatively correlated with PFS, OS and disease control rate (DCR). Higher PLR was also associated with worse OS. In multivariable analysis, neutrophils (p = 0.003), WBC (p = 0.069) and LDH (p = 0.07) maintained their impact on PFS, while OS was affected by LDH (p < 0.001), neutrophils (p < 0.001) and PLR (p = 0.022), while DCR by LDH (p = 0.03) and neutrophils (p = 0.004). In the longitudinal analysis, PFS negatively correlated with higher Δplatelets (p = 0.039), ΔWBC (p < 0.001), and Δneutrophils (p = 0.020), and with lower Δlymphocytes (p < 0.001). Moreover, higher ΔNLR and ΔPLR identified patients with worse PFS, OS and DCR. In the multivariable model, only ΔNLR influenced PFS (p = 0.004), while OS resulted affected by higher ΔWBC (p < 0.001) and lower Δlymphocytes (p = 0.038). Higher ΔWBC also affected the DCR (p = 0.003). When clustering patients in 4 categories using basal LDH and ΔNLR, normal LDH/lower ΔNLR showed a higher PFS than high LDH/higher ΔNLR (20 vs 5 months). Moreover, normal LDH/higher Δlymphocytes had a higher OS than high LDH/lower Δlymphocytes (50 vs. 10 months).
Baseline and early variations of blood cells, together with basal LDH, strongly predict the efficacy of ICI in MM. Our findings propose simple, inexpensive biomarkers for a better selection of patient treatments. Prospective multicenter studies are warranted to confirm these data.
评估基础和一个月时白细胞（WBC）、中性粒细胞、淋巴细胞和血小板值及其比值（中性粒细胞与淋巴细胞比值 NLR 和血小板与淋巴细胞比值 PLR）在预测转移性黑色素瘤（MM）对免疫检查点抑制剂（ICI）反应中的能力。
我们对 272 例接受一线 ICI 治疗的 BRAF 野生型 MM 患者进行了回顾性研究。采用单变量分析将患者/肿瘤特征与临床结局相关联。还计算了血液参数在时间 1 和时间 0 之间的变化（Δ），并使用 ROC 曲线评估的截止值进行了二分类。
在基线时，较高的中性粒细胞和 NLR 与 PFS、OS 和疾病控制率（DCR）呈负相关。较高的 PLR 也与 OS 较差相关。在多变量分析中，中性粒细胞（p=0.003）、WBC（p=0.069）和 LDH（p=0.07）保持对 PFS 的影响，而 OS 受 LDH（p<0.001）、中性粒细胞（p<0.001）和 PLR（p=0.022）的影响，DCR 受 LDH（p=0.03）和中性粒细胞（p=0.004）的影响。在纵向分析中，PFS 与较高的Δ血小板（p=0.039）、ΔWBC（p<0.001）和Δ中性粒细胞（p=0.020）呈负相关，与较低的Δ淋巴细胞（p<0.001）呈负相关。此外，较高的ΔNLR 和ΔPLR 确定了 PFS、OS 和 DCR 较差的患者。在多变量模型中，只有ΔNLR 影响 PFS（p=0.004），而 OS 受较高的ΔWBC（p<0.001）和较低的Δ淋巴细胞（p=0.038）的影响。较高的ΔWBC 也影响 DCR（p=0.003）。当使用基础 LDH 和ΔNLR 将患者聚类为 4 个类别时，正常 LDH/较低ΔNLR 显示出比高 LDH/较高ΔNLR 更高的 PFS（20 个月 vs 5 个月）。此外，正常 LDH/较高Δ淋巴细胞的 OS 高于高 LDH/较低Δ淋巴细胞（50 个月 vs 10 个月）。
基线和早期血细胞变化以及基础 LDH 强烈预测 ICI 在 MM 中的疗效。我们的研究结果提出了简单、廉价的生物标志物，以更好地选择患者的治疗方法。需要进行前瞻性多中心研究来证实这些数据。
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