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
{"title":"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。","authors":"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","doi":"10.1016/j.jtha.2024.10.034","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Objectives: </strong>To evaluate the safety and efficacy of bortezomib in rituximab-refractory iTTP patients.</p><p><strong>Methods: </strong>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).</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":" ","pages":""},"PeriodicalIF":5.5000,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Bortezomib for rituximab-refractory immune-mediated thrombotic thrombocytopenic purpura in the caplacizumab era: an Italian multicenter study.\",\"authors\":\"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\",\"doi\":\"10.1016/j.jtha.2024.10.034\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>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.</p><p><strong>Objectives: </strong>To evaluate the safety and efficacy of bortezomib in rituximab-refractory iTTP patients.</p><p><strong>Methods: </strong>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).</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>Durable responses to bortezomib were registered in about 60% of multirefractory iTTP patients with mild to moderate toxicities. 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Bortezomib for rituximab-refractory immune-mediated thrombotic thrombocytopenic purpura in the caplacizumab era: an Italian multicenter study.
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.
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.