Plataforma de Oncología, Hospital Quironsalud Torrevieja, Torrevieja (Alicante). Spain.
Farm Hosp. 2020 Apr 17;44(3):81-86. doi: 10.7399/fh.11319.
A review of the literature about the anti-programmed death 1 monoclonal antibody nivolumab permits to verify the existence of several issues still unresolved about their dosing schedule. The aim of the present work was to explore possibilities of nivolumab treatment personalization through therapeutic drug monitoring, in order to improve their effectiveness and efficiency.
Observational, prospective study carried out from May 2017 through June 2019 in patients with different tumor diagnoses treated with nivolumab. Blood samples were obtained in the routine clinical practice, once nivolumab steady state was reached. Serum nivolumab levels were determined by means of quantitative ELISA. The standard schedule of 3 mg/kg every two weeks (Q2W) was modified in some patients due to different circumstances, and resulting serum concentrations were compared with those from the non-modified patients and the published data.
Blood samples from 19 patients in treatment with nivolumab were analyzed. A total of 39 samples of nivolumab were analyzed between 6th and 27th cycles. The standard schedule of 3 mg/kg every two weeks was modified in 12/19 (60%) patients, with intervals of 3, 4, 5, 6 or 7 weeks, once the steady state was reached. No statistically significant differences were detected when comparing every two weeks and every four week intervals. When the intervals were six or seven weeks, mean plasma concentration showed a statistically significant difference compared with every two weeks.
Current data contribute to confirm former suspects about the possibilities of exploring new scenarios to improve and personalize nivolumab dosage. Additional studies to confirm it in bigger series and correlate it with clinical results, and to better define the role of therapeutic drug monitoring in the treatment, are warranted, not only by financial concerns but also for improving quality of life of patients and clinical management aspects.
对有关抗程序性死亡 1 单克隆抗体纳武利尤单抗的文献进行综述，可证实其给药方案仍存在若干尚未解决的问题。本研究旨在通过治疗药物监测探索纳武利尤单抗治疗个体化的可能性，以提高其疗效和效率。
这是一项于 2017 年 5 月至 2019 年 6 月期间开展的观察性、前瞻性研究，纳入了不同肿瘤诊断患者接受纳武利尤单抗治疗的病例。在常规临床实践中，当达到纳武利尤单抗稳态时，采集血样。采用定量 ELISA 法测定血清纳武利尤单抗水平。根据不同情况，对部分患者的纳武利尤单抗标准 3mg/kg、每 2 周（Q2W）方案进行了修改，并将所得血清浓度与未修改患者和已发表数据进行了比较。
共分析了 19 例接受纳武利尤单抗治疗患者的血样。共分析了 6 至 27 个周期的 39 个纳武利尤单抗样本。当达到稳态时，19 例患者中有 12 例（60%）修改了纳武利尤单抗标准 3mg/kg、每 2 周方案，间隔分别为 3、4、5、6 或 7 周。当间隔为 4 或 6 周时，与每 2 周方案相比，平均血浆浓度无统计学差异。当间隔为 7 周时，与每 2 周方案相比，差异具有统计学意义。
现有数据有助于证实此前对探索改善和个体化纳武利尤单抗剂量新方案的可能性的猜测。需要进一步开展更大规模的研究来证实这一点，并将其与临床结果相关联，以更好地确定治疗中治疗药物监测的作用，这不仅是出于经济方面的考虑，也是为了提高患者的生活质量和临床管理方面。
