评估一名因接受尼妥珠单抗和伊匹单抗治疗恶性黑色素瘤而出现免疫相关肝毒性的患者暴露于霉酚酸的情况:病例报告。

IF 2.7 4区 医学 Q3 ONCOLOGY Cancer Chemotherapy and Pharmacology Pub Date : 2024-06-01 Epub Date: 2023-12-26 DOI:10.1007/s00280-023-04628-2
Yoshiharu Suzuki, Shingo Ishiguro, Hirokazu Shimada, Masahiro Ohgami, Mika Suzuki
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引用次数: 0

摘要

背景:美国国家综合癌症网络等指南推荐使用霉酚酸酯(MMF)治疗严重的类固醇难治性免疫相关肝毒性。霉酚酸(MPA)是MMF的一种活性形式,可抑制T淋巴细胞和B淋巴细胞增殖以及免疫检查点抑制剂引起的免疫相关不良反应。MPA 的治疗范围较窄(37-70 µg-h/mL),过度暴露会增加移植中白细胞减少的风险。然而,MMF在肿瘤学中的最佳使用方法尚未确定;因此,有必要监测血浆MPA浓度,以避免在肿瘤学实践中出现过度免疫抑制:我们评估了一名 75 岁男性患者的血浆 MPA 浓度,该患者在接受尼妥珠单抗和伊匹单抗联合治疗恶性黑色素瘤后出现了免疫相关肝毒性。患者在接受免疫治疗后出现了严重的肝毒性,并开始使用皮质类固醇进行免疫抑制治疗。随后,患者出现了类固醇难治性免疫相关肝毒性;因此,患者同时服用了 MMF(1000 毫克,每天两次)。服用 MMF 七天后,使用酶乘免疫测定技术测定了血浆中的 MPA 浓度。从 0 到 12 小时,MPA 的血浆浓度-时间曲线下面积为 41.0 µg-h/mL,因此继续服用相同剂量的 MMF。在用药期间,观察到 2 级淋巴细胞减少,这可能是 MMF 引起的。不幸的是,患者感染了 SARS-CoV-2,死于呼吸衰竭:结论:我们的患者没有超过作为肾移植副作用发病指标的 MPA 水平上限,肝功能也得到了迅速改善。在评估类固醇效果后及时开始使用 MMF,可获得足够的 MPA 暴露。使用 MMF 时应考虑进行治疗药物监测,以避免过度暴露。
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Evaluation of mycophenolic acid exposure in a patient with immune-related hepatotoxicity caused by nivolumab and ipilimumab therapy for malignant melanoma: a case report.

Background: Guidelines such as the National Comprehensive Cancer Network recommend mycophenolate mofetil (MMF) for the treatment of severe steroid-refractory immune-related hepatotoxicity. Mycophenolic acid (MPA) is an active form of MMF that suppresses T- and B-lymphocyte proliferation and immune-related adverse events caused by immune checkpoint inhibitors. MPA has a narrow therapeutic range (37-70 µg·h/mL) and overexposure increases the risk of leukopenia in transplantation. However, the optimal use of MMF in oncology has not yet been established; thus, monitoring plasma MPA concentrations is necessary to avoid excessive immunosuppression in oncology practice.

Case presentation: We evaluated plasma MPA concentration in a 75-year-old man with immune-related hepatotoxicity following nivolumab and ipilimumab combination therapy for malignant melanoma. The patient developed severe hepatotoxicity after immunotherapy, and immunosuppressant therapy with corticosteroids was initiated. The patient then developed steroid-refractory immune-related hepatotoxicity; therefore, MMF (1,000 mg twice daily) was co-administered. Seven days after the administration of MMF, the plasma MPA concentration was measured using an enzyme multiplied immunoassay technique. The area under the plasma concentration-time curve for MPA from 0 to 12 h was 41.0 µg·h/mL, and the same dose of MMF was continued. Grade 2 lymphocytopenia, which could be attributed to MMF, was observed during the administration period. Unfortunately, the patient was infected with SARS-CoV-2 and died from respiratory failure.

Conclusion: Our patient did not exceed the upper limit of MPA levels as an index of the onset of side effects of kidney transplantation and achieved rapid improvement in liver function. Prompt initiation of MMF after assessment of the steroid effect leads to adequate MPA exposure. Therapeutic drug monitoring should be considered when MMF is administered, to avoid overexposure.

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来源期刊
CiteScore
6.10
自引率
3.30%
发文量
116
审稿时长
2.5 months
期刊介绍: Addressing a wide range of pharmacologic and oncologic concerns on both experimental and clinical levels, Cancer Chemotherapy and Pharmacology is an eminent journal in the field. The primary focus in this rapid publication medium is on new anticancer agents, their experimental screening, preclinical toxicology and pharmacology, single and combined drug administration modalities, and clinical phase I, II and III trials. It is essential reading for pharmacologists and oncologists giving results recorded in the following areas: clinical toxicology, pharmacokinetics, pharmacodynamics, drug interactions, and indications for chemotherapy in cancer treatment strategy.
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