Bortezomib for rituximab-refractory immune-mediated thrombotic thrombocytopenic purpura in the caplacizumab era: an Italian multicenter study.

IF 5.5 2区 医学 Q1 HEMATOLOGY
Juri Alessandro Giannotta, Andrea Artoni, Ilaria Mancini, Pasquale Agosti, Monica Carpenedo, Addolorata Truma, Syna Miri, Barbara Ferrari, Pasqualina De Leo, Prassede Salutari, Giorgia Mancini, Alfredo Molteni, Ermina Rinaldi, Monica Bocchia, Mariasanta Napolitano, Lucia Prezioso, Annarosa Cuccaro, Elisabetta Scarpa, Annalisa Condorelli, Daniele Grimaldi, Massimo Massaia, Flora Peyvandi
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引用次数: 0

Abstract

Background: Immune-mediated thrombotic thrombocytopenic purpura (iTTP) patients are not responsive to standard rituximab in approximately 10% to 15% of cases, and oral immunosuppressants showed controversial results with significant toxicity. Targeting plasma cells with bortezomib appears promising, but the available evidence is scarce and stems only from isolated reports in the precaplacizumab era.

Objectives: To evaluate the safety and efficacy of bortezomib in rituximab-refractory iTTP patients.

Methods: We conducted a retrospective observational multicenter study among 13 Italian iTTP treating centers, collecting data from May 2017 to May 2023 (caplacizumab was licensed in Italy in January 2020).

Results: Bortezomib was effective in 10/17 patients (59%). Eleven were treated in the acute phase (9/11 responders, 82%, allowing discontinuation of caplacizumab in 5/6 treated patients), and 7 during clinical remission (2/7 responders, 28%). Responses occurred at a median time of 30 days, but 3 patients responded after 4 months. The median duration of response was 22 months (IQR, 10-38), still ongoing in 6 patients at the time of data cutoff. Responders had fewer previous acute iTTP episodes than nonresponders (median [IQR], 1 [1,2] vs 5.5 [2-7]; P = .03). Eight subjects (47%) reported toxicities, mostly in those treated with ≥2 cycles.

Conclusion: Durable responses to bortezomib were registered in about 60% of multirefractory iTTP patients with mild to moderate toxicities. The occurrence of late responses (ie, after 30 days) suggests a "watchful waiting" approach after bortezomib treatment.

硼替佐米治疗利妥昔单抗难治性免疫介导的血栓性血小板减少性紫癜:一项意大利多中心研究。
背景:免疫介导的血栓性血小板减少性紫癜(iTTP)患者中约有10%-15%对标准利妥昔单抗无反应,口服免疫抑制剂的效果存在争议,且毒性较大。硼替佐米靶向浆细胞似乎很有前景,但现有证据很少,而且仅来自于卡帕珠单抗时代之前的个别报道:评估硼替佐米在利妥昔单抗难治性 iTTP 患者中的安全性和有效性:我们在13个意大利iTTP治疗中心开展了一项回顾性多中心观察研究,收集了2017年5月至2023年5月(2020年1月卡普珠单抗在意大利获得许可)的数据:硼替佐米对10/17例患者(59%)有效。其中11例在急性期接受治疗(9/11例应答,占82%,5/6例接受治疗的患者可停用卡普珠单抗),7例在临床缓解期接受治疗(2/7例应答,占28%)。出现应答的中位时间为 30 天,但有 3 名患者在 4 个月后才出现应答。中位应答持续时间为 22 个月(IQR 10-38),数据截止时仍有 6 名患者在应答中。与非应答者相比,应答者既往急性 iTTP 发作次数较少[中位数(IQR)1(1-2) vs 5.5(2-7),P=0.03]。8名受试者(47%)报告了毒性反应,其中大部分是接受了≥2个周期治疗的受试者:结论:约60%的多重难治性iTTP患者对硼替佐米产生了持久的应答,毒性反应轻微至中等。晚期反应(即 30 天后)的出现表明,硼替佐米治疗后应采取 "观察等待 "的方法。
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来源期刊
Journal of Thrombosis and Haemostasis
Journal of Thrombosis and Haemostasis 医学-外周血管病
CiteScore
24.30
自引率
3.80%
发文量
321
审稿时长
1 months
期刊介绍: The Journal of Thrombosis and Haemostasis (JTH) serves as the official journal of the International Society on Thrombosis and Haemostasis. It is dedicated to advancing science related to thrombosis, bleeding disorders, and vascular biology through the dissemination and exchange of information and ideas within the global research community. Types of Publications: The journal publishes a variety of content, including: Original research reports State-of-the-art reviews Brief reports Case reports Invited commentaries on publications in the Journal Forum articles Correspondence Announcements Scope of Contributions: Editors invite contributions from both fundamental and clinical domains. These include: Basic manuscripts on blood coagulation and fibrinolysis Studies on proteins and reactions related to thrombosis and haemostasis Research on blood platelets and their interactions with other biological systems, such as the vessel wall, blood cells, and invading organisms Clinical manuscripts covering various topics including venous thrombosis, arterial disease, hemophilia, bleeding disorders, and platelet diseases Clinical manuscripts may encompass etiology, diagnostics, prognosis, prevention, and treatment strategies.
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