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对免疫调节剂过敏患者的泊马度胺脱敏治疗

Pomalidomide desensitization in a patient hypersensitive to immunomodulating agents.

作者信息

Seki J T, Sakurai N, Lam W, Reece D E

机构信息

Department of Pharmacy, Princess Margaret Cancer Centre, University Health Network.

Leslie Dan Faculty of Pharmacy, University of Toronto; and.

出版信息

Curr Oncol. 2017 Aug;24(4):e328-e332. doi: 10.3747/co.24.3572. Epub 2017 Aug 31.

Abstract

Despite progressive treatments with tandem stem-cell transplantation, patients with incurable myeloma eventually succumb to relapsed or refractory disease if left untreated. Promising agents such as proteasome inhibitors and immunomodulating imide drugs (imids), including the newer-generation agent pomalidomide, in combination with lower-dose dexamethasone, have been shown to be effective and to significantly improve and prolong survival in pretreated patients. Although the incidence of pomalidomide hypersensitivity reaction (hsr) in this class of drugs is not as well known, we have documented cutaneous toxicity (grade 3 by the version 4) in 2 separate cases (not yet published). Because the imids are chemically, structurally, and pharmacologically similar, it is not unreasonable to consider possible cross-reactivity in pomalidomide recipients who developed hsr when receiving previous lines of imids. As a patient's advocate, it is only prudent to provide a responsible, and yet practical, means to better address cross-sensitivity for patients. Intervention with the use of a rapid desensitization program (rdp) as a preventive measure should be introduced before initiating pomalidomide. Such a proactive measure for the patient's safety will ensure a smooth transition into pomalidomide treatment. A hsr can be either related or non-related to immunoglobulin E. As imids become an essential treatment backbone for myeloma and other plasma-cell diseases, an increasing number of patients could experience skin and other life-threatening toxicities, resulting in unnecessary discontinuation of these life-prolonging agents. An extemporaneously prepared pomalidomide suspension developed at our centre enables patients to undergo rdp safely. Patients enjoy a good quality of life and clinical response after the rdp procedure.

摘要

尽管采用串联干细胞移植进行了渐进性治疗,但无法治愈的骨髓瘤患者如果不接受治疗,最终会死于复发或难治性疾病。蛋白酶体抑制剂和免疫调节性酰亚胺药物(IMiDs)等有前景的药物,包括新一代药物泊马度胺,与低剂量地塞米松联合使用,已被证明在预处理患者中有效,并能显著改善和延长生存期。虽然这类药物中泊马度胺过敏反应(HSR)的发生率尚不为人所知,但我们在2例单独病例中记录了皮肤毒性(根据第4版为3级)(尚未发表)。由于IMiDs在化学、结构和药理上相似,对于在接受先前几线IMiDs时发生HSR的泊马度胺接受者,考虑可能的交叉反应是合理的。作为患者的支持者,提供一种负责任且实用的方法来更好地应对患者的交叉敏感性是谨慎之举。在开始使用泊马度胺之前,应引入使用快速脱敏方案(RDP)作为预防措施进行干预。这种为患者安全采取的积极措施将确保顺利过渡到泊马度胺治疗。HSR可能与免疫球蛋白E相关或不相关。随着IMiDs成为骨髓瘤和其他浆细胞疾病的重要治疗支柱,越来越多的患者可能会出现皮肤和其他危及生命的毒性反应,导致这些延长生命的药物不必要地停用。我们中心研发的一种临时配制泊马度胺混悬液能使患者安全地进行RDP。RDP程序后患者生活质量良好且有临床反应。

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本文引用的文献

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Progress and Paradigms in Multiple Myeloma.多发性骨髓瘤的进展与范式
Clin Cancer Res. 2016 Nov 15;22(22):5419-5427. doi: 10.1158/1078-0432.CCR-16-0625.
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The safety of pomalidomide for the treatment of multiple myeloma.泊马度胺治疗多发性骨髓瘤的安全性。
Expert Opin Drug Saf. 2016;15(4):535-47. doi: 10.1517/14740338.2016.1154039. Epub 2016 Mar 16.
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Multiple Myeloma: Diagnosis and Treatment.多发性骨髓瘤:诊断与治疗
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