Therapeutic drug monitoring enables safe and effective lenalidomide therapy in patients with multiple myeloma on hemodialysis
Therapeutic drug monitoring enables safe and effective lenalidomide therapy in patients with multiple myeloma on hemodialysis
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治疗药物监测使血液透析的多发性骨髓瘤患者能够安全有效地接受来那度胺治疗
DOI：
10.1007/s00277-016-2809-5
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发表时间：
2016
期刊：
影响因子：
3.5
通讯作者：
Naoto Takahashi
中科院分区：
文献类型：
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作者：
Takahiro Kobayashi;Takenori Niioka;Masatomo Miura;Naoto Takahashi
尊敬的编辑，João等人。强调了在多发性骨髓瘤(MM)和肾损害(RI)患者初始剂量设定后，根据个体耐受性持续调整来那度胺(LEN)剂量的必要性，因为LEN是从尿液中排泄的[1]。随着RI的进展，LEN的浓度-时间曲线下面积(AUC)增加，LEN的血浆半衰期(T1/2)也延长[2]。目前，在RI中，LEN的剂量调整是基于旨在达到类似AUC水平并保持低谷浓度以限制毒性的数据。然而，这些数据来自非癌症患者；据我们所知，没有关于血液透析(HD)的MM患者的Len尿排泄率的报告。我们分析了两例多发性骨髓瘤患者血液透析时的血药浓度和尿量，以避免毒性反应，从而确定血液透析中合适的LEN用量。病例1为45岁女性，体重40公斤。肌酐清除量(CrCl)为8mL/min，中位尿量为2.56mL/d。根据最初的剂量建议，LEN在透析后每周三次，剂量为5毫克。然而，由于Len过量服用，这导致了发热性中性粒细胞减少症和感染性休克。因此，我们将LEN剂量减少到每周5毫克，并监测血浆浓度；在第7天证实完全消除，没有毒性(图1)。例2为78岁男性，红细胞输注依赖，体重61公斤。CRCL为7毫升/分，中位尿量为200毫升/天。虽然LEN的初始剂量为5 mg，每周3次，但根据病例1的经验，患者每周服用LEN 5 mg加地塞米松20 mg。治疗2周后，他不再需要输血；单抗蛋白水平也从2380 mg/dL下降到1633 mg/dL，没有明显的毒性。血液透析前后的血浆样本和累积的尿样被收集，并使用如上所述的液相色谱-串联质谱仪进行分析[3]。两个病例在1周后都检测不到LEN的血浆浓度(图1)。病例1和病例2的平均消除时间t1/2分别为31.6h和44.7h。病例1和病例2的尿液中LEN累积回收率分别为1.9%和40.3%，两者差异显著，因为病例2的中位数尿量是病例1的80倍(图1)。根据RI调整Len的剂量对于减少毒性很重要[4]。虽然根据建议设置初始剂量是有用的，但这是不可接受的，正如病例1的严重毒性所表明的那样。这些发现表明，即使LEN的最大浓度不受影响
Dear Editor, João et al. emphasized the necessity of continuous dose adjustment of lenalidomide (Len) according to individual tolerance after initial dose setting in patients with multiple myeloma (MM) and renal impairment (RI), because Len is excreted in urine [1]. As RI progresses, the area under the concentration-time curve (AUC) of Len increases, and the plasma half-life (t1/2) of Len is also prolonged [2]. Currently, dose adjustment of Len in RI is based on data aimed at achieving similar AUC levels and maintaining low trough concentrations to limit toxicity. However, these are data from non-cancer patients; to our knowledge, there are no reports of Len urinary excretion rate in MM patients on hemodialysis (HD). We analyzed the plasma concentration and urinary volume of Len in two patients with MM on HD to avoid toxicity and to determine the appropriate Len dosage in HD. Case 1 was a 45-year-old woman with a body weight of 40 kg. Creatinine clearance (CrCl) was 8 mL/min and median urine volume was 2.56 mL/day. Len was administered at a dose of 5 mg three times a week following dialysis, in accordance with initial dose recommendations. However, this led to febrile neutropenia and septic shock due to Len overdosing. Hence, we reduced the dose to Len 5 mg weekly and monitored plasma concentration; complete elimination was confirmed on day 7, with no toxicity (Fig. 1). Case 2 was a 78-year-old man with red blood cell transfusion-dependence and body weight of 61 kg. CrCl was 7 mL/min and median urine volume was 200 mL/day. Although the initial dose of Len according to the recommendation was 5 mg three times a week, the patient was given Len 5 mg plus dexamethasone 20 mg once a week based on the experience with Case 1. After 2 weeks of therapy, he no longer needed blood transfusion; monoclonal protein levels also declined from 2380 to 1633 mg/dL, and there was no obvious toxicity. Plasma samples from venipuncture before and after HD and cumulative urine samples were collected and analyzed using liquid chromatography-tandem mass spectrometry as previously described [3]. Plasma concentration of Len was undetectable in both cases after 1 week (Fig. 1). The mean elimination t1/2 of Len was 31.6 h in Case 1 and 44.7 h in Case 2. Cumulative recovery rate of Len in urine differed dramatically (1.9 and 40.3% in Cases 1 and 2, respectively) because median urine volume in Case 2 was 80 times greater than that in Case 1 even though both patients were on HD (Fig. 1). Dose adjustment of Len according to RI is important to reduce toxicity [4]. Although it is useful to set the initial dose according to the recommendation, this is not acceptable, as indicated by severe toxicity in Case 1. These findings suggest that even though Len maximum concentration is not influenced
用于估计多发性骨髓瘤患者来那度胺暴露量的有限采样模型
DOI：
--
发表时间：
2015
期刊：
--
影响因子：
--
作者：
志田 青慈
通讯作者：
志田 青慈