Sriram Ravichandran, Andrew Hall, Matthew Jenner, Mamta Garg, Bhuvan Kishore, Helen Lachmann, Julian Gillmore, Alexandra Pitchford, Jamie B Oughton, Shameem Mahmood, Sajitha Sachchithantham, Philip Hawkins, Sarah Brown, Ashutosh Wechalekar
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Here, we report the results of a phase Ib dose-escalation study of Carfilzomib-Thalidomide-Dexamethasone (KTD) in relapsed/refractory AL amyloidosis.</p><p><strong>Results: </strong>The trial registered 11 patients from 6 UK centres from September 2017 to January 2019; 10 patients received at least one dose of trial treatment. 80 adverse events were reported from 10 patients in the 1<sup>st</sup> three cycles. One patient experienced dose-limiting toxicity (acute kidney injury) at a dose of 45 mg/m<sup>2,</sup> and another patient had a SAR (fever). Five patients experienced an AE ≥ grade 3. There were no haematologic, infectious, or cardiac AE ≥ grade 3. The overall haematological response rate (ORR) at the end of three cycles of treatment was 60%.</p><p><strong>Conclusion: </strong>Carfilzomib 45 mg/m<sup>2</sup> weekly can be safely given with thalidomide and dexamethasone. The efficacy and tolerability profile appears comparable to other agents in relapsed AL amyloidosis. These data provide a framework for further studies of carfilzomib combinations in AL amyloidosis.</p>","PeriodicalId":50964,"journal":{"name":"Amyloid-Journal of Protein Folding Disorders","volume":"30 3","pages":"290-296"},"PeriodicalIF":5.2000,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"A phase 1b dose-escalation study of carfilzomib in combination with thalidomide and dexamethasone in patients with relapsed/refractory systemic immunoglobulin light chain amyloidosis.\",\"authors\":\"Sriram Ravichandran, Andrew Hall, Matthew Jenner, Mamta Garg, Bhuvan Kishore, Helen Lachmann, Julian Gillmore, Alexandra Pitchford, Jamie B Oughton, Shameem Mahmood, Sajitha Sachchithantham, Philip Hawkins, Sarah Brown, Ashutosh Wechalekar\",\"doi\":\"10.1080/13506129.2023.2169124\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Introduction: </strong>Proteasome inhibitors are the backbone of AL amyloidosis treatment - bortezomib being most widely used. 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引用次数: 0
摘要
简介蛋白酶体抑制剂是治疗肌萎缩性淀粉样变性的主要药物，其中硼替佐米的应用最为广泛。卡非佐米是一种获准用于治疗多发性骨髓瘤的蛋白酶体抑制剂；自主神经和周围神经病变是卡非佐米不常见的毒性反应。卡非佐米用于 AL 淀粉样变性的数据有限。在此，我们报告了卡非佐米-他利度胺-地塞米松（KTD）治疗复发/难治性AL淀粉样变性的Ib期剂量递增研究结果：2017年9月至2019年1月，该试验登记了来自英国6个中心的11名患者；10名患者接受了至少一个剂量的试验治疗。10名患者在前三个周期中报告了80例不良事件。一名患者在剂量为45 mg/m2时出现剂量限制性毒性（急性肾损伤），另一名患者出现SAR（发热）。五名患者的 AE ≥ 3 级。没有血液学、感染性或心脏毒性反应≥3级。三个治疗周期结束时的总体血液学应答率（ORR）为60%：结论：卡非佐米每周45毫克/平方米的剂量可与沙利度胺和地塞米松一起安全使用。对于复发的AL淀粉样变性病，其疗效和耐受性似乎与其他药物相当。这些数据为进一步研究卡非佐米联合治疗AL淀粉样变性病提供了框架。
A phase 1b dose-escalation study of carfilzomib in combination with thalidomide and dexamethasone in patients with relapsed/refractory systemic immunoglobulin light chain amyloidosis.
Introduction: Proteasome inhibitors are the backbone of AL amyloidosis treatment - bortezomib being most widely used. Carfilzomib is a proteasome inhibitor licenced to treat multiple myeloma; autonomic and peripheral neuropathy are uncommon toxicities with carfilzomib. There is limited data on the use of carfilzomib in AL amyloidosis. Here, we report the results of a phase Ib dose-escalation study of Carfilzomib-Thalidomide-Dexamethasone (KTD) in relapsed/refractory AL amyloidosis.
Results: The trial registered 11 patients from 6 UK centres from September 2017 to January 2019; 10 patients received at least one dose of trial treatment. 80 adverse events were reported from 10 patients in the 1st three cycles. One patient experienced dose-limiting toxicity (acute kidney injury) at a dose of 45 mg/m2, and another patient had a SAR (fever). Five patients experienced an AE ≥ grade 3. There were no haematologic, infectious, or cardiac AE ≥ grade 3. The overall haematological response rate (ORR) at the end of three cycles of treatment was 60%.
Conclusion: Carfilzomib 45 mg/m2 weekly can be safely given with thalidomide and dexamethasone. The efficacy and tolerability profile appears comparable to other agents in relapsed AL amyloidosis. These data provide a framework for further studies of carfilzomib combinations in AL amyloidosis.
期刊介绍：
Amyloid: the Journal of Protein Folding Disorders is dedicated to the study of all aspects of the protein groups and associated disorders that are classified as the amyloidoses as well as other disorders associated with abnormal protein folding. The journals major focus points are:
etiology,
pathogenesis,
histopathology,
chemical structure,
nature of fibrillogenesis;
whilst also publishing papers on the basic and chemical genetic aspects of many of these disorders.
Amyloid is recognised as one of the leading publications on amyloid protein classifications and the associated disorders, as well as clinical studies on all aspects of amyloid related neurodegenerative diseases and major clinical studies on inherited amyloidosis, especially those related to transthyretin. The Journal also publishes book reviews, meeting reports, editorials, thesis abstracts, review articles and symposia in the various areas listed above.
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