Nivolumab for advanced melanoma: pretreatment prognostic factors and early outcome markers during therapy.
Nivolumab for advanced melanoma: pretreatment prognostic factors and early outcome markers during therapy.
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DOI：
10.18632/oncotarget.12677
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发表时间：
2016-11-22
期刊：
影响因子：
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通讯作者：
Yamazaki N
中科院分区：
文献类型：
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作者：
Nakamura Y;Kitano S;Takahashi A;Tsutsumida A;Namikawa K;Tanese K;Abe T;Funakoshi T;Yamamoto N;Amagai M;Yamazaki N
抗程序性细胞死亡蛋白 1 单克隆抗体纳武单抗 (nivolumab) 是治疗晚期黑色素瘤最有效的药物之一。肿瘤细胞衍生或免疫细胞衍生的标记物和临床预测因子，例如血清乳酸脱氢酶（LDH）和皮肤不良事件，已被描述为纳武单抗治疗的晚期黑色素瘤的预后因素。我们试图确定可以在常规临床实践中确定的进一步临床预测因素。我们回顾性分析了 2014 年 7 月至 2016 年 7 月期间在日本东京国立癌症中心医院或庆应义塾大学医院接受纳武利尤单抗治疗的连续 98 名不可切除的 III 期或 IV 期黑色素瘤患者的临床结果。这些患者每 3 周接受 2 毫克/公斤剂量的纳武利尤单抗治疗。至于治疗前的预后因素，ECOG表现状态（PS）≥1、最大肿瘤直径≥30mm、LDH升高和C反应蛋白升高与总生存期（OS）不良显着相关（风险比[HR] 0.29 [P<0.001]、HR 0.40 [p=0.003]、HR 0.29 [P<0.001]、HR 0.42 [P=0.004]，分别）单变量分析。在这些因素中，通过多变量分析将PS和LDH确定为自变量。至于治疗期间检查的早期标志物，绝对淋巴细胞计数（ALC）≥1000/μl（第3周：HR 0.40[P=0.004]，第6周：HR 0.33[P=0.001]）和绝对中性粒细胞计数（ANC）<4000/μl（第3周：HR 0.46[P=0.014]，第6周：HR 0.51）的患者[P=0.046]）的 OS 明显更好。治疗期间 ALC≥1000/μl 和 ANC<4000/μl 似乎是与 OS 相关的早期标志物。纳武单抗对于肿瘤负荷较大的患者可能疗效甚微。
An anti-programmed cell death protein 1 monoclonal antibody, nivolumab, is one of the most effective drugs for advanced melanoma. Tumor cell-derived or immune cell-derived markers and clinical predictors such as serum lactate dehydrogenase (LDH) and cutaneous adverse events, have already been described as prognostic factors for advanced melanoma treated with nivolumab. We sought to identify further clinical predictors that can be determined in routine clinical practice. We retrospectively analyzed clinical findings of 98 consecutive patients with unresectable stage III or IV melanoma treated with nivolumab, at the National Cancer Center Hospital or at Keio University Hospital, in Tokyo, Japan, between July 2014 and July 2016. These patients had been administered nivolumab at a dose of 2mg/kg every 3 weeks. As for pretreatment prognostic factors, ECOG performance status (PS) ≥1, maximum tumor diameters of ≥30mm, elevated LDH and elevated C-reactive protein were significantly associated with poor overall survival (OS) (hazard ratio [HR] 0.29 [P<0.001], HR 0.40 [p=0.003], HR 0.29 [P<0.001], HR 0.42 [P=0.004], respectively) on univariate analysis. Among these factors, PS and LDH were identified as independent variables by multivariate analysis. As for early markers examined during therapy, patients with absolute lymphocyte count (ALC) ≥ 1000/μl (Week3: HR 0.40 [P=0.004], Week6: HR 0.33 [P=0.001]) and absolute neutrophil count (ANC) <4000/μl (Week3: HR 0.46 [P=0.014], Week6: HR 0.51 [P=0.046]) had significantly better OS. ALC≥1000/μl and ANC<4000/μl during treatment appear to be early markers associated with OS. Nivolumab might have minimal efficacy in patients with a massive tumor burden.