Urology, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, Japan.
Urology, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, Japan
J Immunother Cancer. 2021 Feb;9(2). doi: 10.1136/jitc-2020-001564.
The dynamic change in C-reactive protein (CRP) levels, CRP kinetics, is a prognostic factor for metastatic renal cell carcinoma (mRCC) in the tyrosine kinase inhibitor era. We investigated the impact of early CRP kinetics on the efficacy of nivolumab in patients with mRCC.
We performed a retrospective analysis of 42 mRCC patients who were treated with nivolumab as a second-line or later therapy between 2016 and 2019. All patients had received previous TKI therapy. Patients were divided into three groups based on their early CRP kinetics: CRP levels increased to more than double compared with baseline within 1 month after initiation of nivolumab (flare) and then decreased to a lower value than baseline within 3 months (CRP flare-responders); CRP levels decreased by ≥30% within 3 months without "flare" (CRP responders); and the remaining patients (non-CRP responders). The maximum tumor shrinkage, objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) were evaluated. The association of the early CRP kinetics and oncological outcomes was assessed.
The median follow-up period was 8 months. The median baseline CRP level was 23 mg/L. CRP flare-responders, CRP responders, and non-CRP responders included 11 (26%), 15 (36%), and 16 (38%) patients, respectively. Thirteen patients (31%) died of mRCC. The maximum changes in target lesions from baseline of CRP flare-responder, CRP-responder, and non-CRP responder groups were -38%, -13%, and 16%, on average, respectively (p<0.001). ORRs of these three groups were 73%, 27%, and 6%, respectively (p<0.001). The median PFS values of each group were not reached, 12 months, and 2.4 months (p=0.005), and the median OS values were not reached, not reached, and 12 months (p=0.048). In a multivariate analysis, early CRP kinetics was a significant independent factor for objective response, PFS, and OS (p<0.001, p=0.004, and p=0.006, respectively).
CRP flare-response was associated with significant tumor shrinkage and improved survival outcomes in patients with mRCC who were treated with nivolumab. Early CRP kinetics could be useful for evaluating nivolumab treatment efficacy.
C 反应蛋白（CRP）水平的动态变化，即 CRP 动力学，是酪氨酸激酶抑制剂时代转移性肾细胞癌（mRCC）的预后因素。我们研究了早期 CRP 动力学对 mRCC 患者接受纳武利尤单抗治疗疗效的影响。
我们对 2016 年至 2019 年间接受纳武利尤单抗二线或后线治疗的 42 例 mRCC 患者进行了回顾性分析。所有患者均接受过先前的 TKI 治疗。根据患者纳武利尤单抗治疗后早期 CRP 动力学，将患者分为三组：纳武利尤单抗治疗后 1 个月内 CRP 水平较基线升高超过两倍（flare），且 3 个月内降至低于基线水平（CRP flare-responders）；3 个月内 CRP 下降≥30%且无“flare”（CRP responders）；其余患者（非 CRP responders）。评估最大肿瘤退缩、客观缓解率（ORR）、无进展生存期（PFS）和总生存期（OS）。评估早期 CRP 动力学与肿瘤学结局的相关性。
中位随访时间为 8 个月。中位基线 CRP 水平为 23mg/L。CRP flare-responders、CRP responders 和非 CRP responders 组分别包括 11 例（26%）、15 例（36%）和 16 例（38%）患者。13 例（31%）患者死于 mRCC。CRP flare-responder、CRP-responder 和 non-CRP responder 组的目标病灶从基线的最大变化分别为平均 -38%、-13%和 16%（p<0.001）。三组的 ORR 分别为 73%、27%和 6%（p<0.001）。各组中位 PFS 值分别为未达到、12 个月和 2.4 个月（p=0.005），中位 OS 值分别为未达到、未达到和 12 个月（p=0.048）。多变量分析显示，早期 CRP 动力学是客观反应、PFS 和 OS 的显著独立因素（p<0.001、p=0.004 和 p=0.006）。
在接受纳武利尤单抗治疗的 mRCC 患者中，CRP flare- response 与明显的肿瘤退缩和生存改善相关。早期 CRP 动力学可能有助于评估纳武利尤单抗治疗的疗效。
