Dynamics of clinical biomarkers as predictors of immunotherapy benefit in metastatic melanoma patients
Dynamics of clinical biomarkers as predictors of immunotherapy benefit in metastatic melanoma patients
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DOI：
10.1007/s12094-020-02420-9
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发表时间：
2020-06-19
影响因子：
3.4
通讯作者：
Munoz-Couselo, E.
中科院分区：
文献类型：
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作者：
Hernando-Calvo, A.;Garcia-Alvarez, A.;Munoz-Couselo, E.
目的基线LDH、推导的中性粒细胞-淋巴细胞比率（dNLR）和免疫相关不良事件（irAE）与转移性黑色素瘤（MM）患者的结局相关。我们假设LDH、dNLR的动态变化和irAE的发生率是否可能影响抗CTLA 4或抗PD 1单药治疗MM患者的预后。方法回顾性分析MM患者病历，前瞻性监测dNLR、LDH值及irAE发生率。主要终点为总生存期（OS）。结果在第2周期结束时，从高dNLR（>= 2.5）转换为低dNLR（HR：0.14; 0.03-0.74;p = 0.02）或从高LDH（>= 1.5 x ULN）转换为低LDH水平（HR：0.08; 0.01-0.68;p = 0.02）的患者的OS显著优于dNLR或LDH评分较高的患者。与未发生irAE的患者相比，在发生irAE ≥ 2级的患者中也观察到OS更长（HR：0.2; 0.05-0.89;p = 0.03）。结论：我们发现dNLR和LDH指标从基线到第2周期的主要变化以及从基线到第2周期的变化与接受单药抗PD 1治疗的MM患者的OS显著相关。实验室变化和临床变量可能有助于优化预后估计。
Purpose Baseline LDH, derived neutrophil-lymphocyte ratio (dNLR) and immune-related adverse events (irAEs) are associated with outcomes of patients with metastatic melanoma (MM). We hypothesized whether dynamic shifts in LDH, dNLR and incidence of irAEs may impact the prognosis of MM patients treated with anti-CTLA4 or anti-PD1 as single agents. Methods Retrospective analysis of medical charts from MM patients with prospective monitoring of dNLR, LDH values and irAE incidence. Primary endpoint was overall survival (OS). Results Patients switching from either high dNLR (>= 2.5) to low dNLR (HR: 0.14; 0.03-0.74;p = 0.02) or high LDH (>= 1.5 x ULN) to low LDH levels (HR: 0.08; 0.01-0.68;p = 0.02) had significantly better OS than those with high dNLR or LDH scores at the end of cycle 2. Longer OS was also observed in patients developing irAEs >= grade 2 as compared to no irAEs (HR: 0.2; 0.05-0.89;p = 0.03). Conclusions We found that major shifts in dNLR and LDH measures from baseline to cycle 2 measures and shifts from baseline to cycle 2 are significantly associated with OS in MM patients receiving single agent anti-PD1 therapy. Laboratory changes and clinical variables may help optimize prognostic estimates.