Pub Date : 2024-09-01Epub Date: 2024-07-18DOI: 10.1016/S2352-3026(24)00185-6
Rena Buckstein
{"title":"SintraREViewed: practice changing, or validation required?","authors":"Rena Buckstein","doi":"10.1016/S2352-3026(24)00185-6","DOIUrl":"10.1016/S2352-3026(24)00185-6","url":null,"abstract":"","PeriodicalId":48726,"journal":{"name":"Lancet Haematology","volume":" ","pages":"e632-e634"},"PeriodicalIF":15.4,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141735434","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-01Epub Date: 2024-08-05DOI: 10.1016/S2352-3026(24)00223-0
Glenn F Pierce, Brian O'Mahony, Radoslaw Kaczmarek, Mark W Skinner, Mike Makris, Flora Peyvandi, Alok Srivastava, Cedric Hermans
{"title":"Risk of harm to people with haemophilia from the 2023 WHO Essential Medicines List.","authors":"Glenn F Pierce, Brian O'Mahony, Radoslaw Kaczmarek, Mark W Skinner, Mike Makris, Flora Peyvandi, Alok Srivastava, Cedric Hermans","doi":"10.1016/S2352-3026(24)00223-0","DOIUrl":"10.1016/S2352-3026(24)00223-0","url":null,"abstract":"","PeriodicalId":48726,"journal":{"name":"Lancet Haematology","volume":" ","pages":"e638-e640"},"PeriodicalIF":15.4,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141908059","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-01Epub Date: 2024-07-18DOI: 10.1016/S2352-3026(24)00186-8
Niels W C J van de Donk, Ajai Chari, Maria Victoria Mateos
Off-the-shelf T-cell-redirecting bispecific antibodies targeting BCMA, GPRC5D, and FcRH5 have high activity in multiple myeloma with a manageable toxicity profile. However, not all patients respond to bispecific antibodies and patients can develop bispecific antibody resistance after an initial response. Mechanisms that contribute to bispecific antibody resistance are multifactorial and include tumour-related factors, such as high tumour burden, expression of T-cell inhibitory ligands, and antigen loss. Resistance due to antigen escape can be prevented by simultaneously targeting two tumour-associated antigens with a trispecific antibody or a combination of two bispecific antibodies. There is also increasing evidence that primary resistance to bispecific antibodies is associated with impaired baseline T-cell function. Long-term exposure to bispecific antibodies with chronic T-cell stimulation further aggravates T-cell dysfunction, which could contribute to failure of disease control. Therapeutic interference with T-cell exhaustion by targeting inhibitory or costimulatory pathways could improve bispecific antibody-mediated antitumour activity. The immunosuppressive microenvironment also contributes to bispecific antibody resistance. CD38-targeting antibodies hold promise as combination partners for bispecific antibodies because of their potential to eliminate CD38+ immune suppressor cells. In conclusion, a better understanding of the mechanisms underlying the absence of disease response has provided novel insights to optimise T-cell activity and bispecific antibody efficacy in multiple myeloma.
以 BCMA、GPRC5D 和 FcRH5 为靶点的现成 T 细胞重定向双特异性抗体对多发性骨髓瘤有很高的活性，毒性也在可控范围内。然而，并非所有患者都对双特异性抗体有反应，而且患者在初次反应后可能会产生双特异性抗体抗药性。导致双特异性抗体耐药的机制是多因素的，包括肿瘤相关因素，如肿瘤负荷高、T细胞抑制配体的表达和抗原丢失。通过使用三特异性抗体或两种双特异性抗体的组合同时靶向两种肿瘤相关抗原，可以防止因抗原丢失而产生的抗药性。越来越多的证据表明，双特异性抗体的原发性抗药性与基线 T 细胞功能受损有关。长期接触双特异性抗体和慢性 T 细胞刺激会进一步加重 T 细胞功能障碍，从而导致疾病控制失败。通过靶向抑制或成本刺激途径来治疗T细胞衰竭，可以提高双特异性抗体介导的抗肿瘤活性。免疫抑制微环境也是造成双特异性抗体抗药性的原因之一。CD38 靶向抗体有望成为双特异性抗体的组合伙伴，因为它们具有消除 CD38+ 免疫抑制细胞的潜力。总之，更好地了解疾病无反应的机制为优化多发性骨髓瘤的T细胞活性和双特异性抗体疗效提供了新的见解。
{"title":"Mechanisms of resistance against T-cell engaging bispecific antibodies in multiple myeloma: implications for novel treatment strategies.","authors":"Niels W C J van de Donk, Ajai Chari, Maria Victoria Mateos","doi":"10.1016/S2352-3026(24)00186-8","DOIUrl":"10.1016/S2352-3026(24)00186-8","url":null,"abstract":"<p><p>Off-the-shelf T-cell-redirecting bispecific antibodies targeting BCMA, GPRC5D, and FcRH5 have high activity in multiple myeloma with a manageable toxicity profile. However, not all patients respond to bispecific antibodies and patients can develop bispecific antibody resistance after an initial response. Mechanisms that contribute to bispecific antibody resistance are multifactorial and include tumour-related factors, such as high tumour burden, expression of T-cell inhibitory ligands, and antigen loss. Resistance due to antigen escape can be prevented by simultaneously targeting two tumour-associated antigens with a trispecific antibody or a combination of two bispecific antibodies. There is also increasing evidence that primary resistance to bispecific antibodies is associated with impaired baseline T-cell function. Long-term exposure to bispecific antibodies with chronic T-cell stimulation further aggravates T-cell dysfunction, which could contribute to failure of disease control. Therapeutic interference with T-cell exhaustion by targeting inhibitory or costimulatory pathways could improve bispecific antibody-mediated antitumour activity. The immunosuppressive microenvironment also contributes to bispecific antibody resistance. CD38-targeting antibodies hold promise as combination partners for bispecific antibodies because of their potential to eliminate CD38<sup>+</sup> immune suppressor cells. In conclusion, a better understanding of the mechanisms underlying the absence of disease response has provided novel insights to optimise T-cell activity and bispecific antibody efficacy in multiple myeloma.</p>","PeriodicalId":48726,"journal":{"name":"Lancet Haematology","volume":" ","pages":"e693-e707"},"PeriodicalIF":15.4,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141735431","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-01Epub Date: 2024-07-18DOI: 10.1016/S2352-3026(24)00172-8
William G Wierda, Nirav N Shah, Chan Y Cheah, David Lewis, Marc S Hoffmann, Catherine C Coombs, Nicole Lamanna, Shuo Ma, Deepa Jagadeesh, Talha Munir, Yucai Wang, Toby A Eyre, Joanna M Rhodes, Matthew McKinney, Ewa Lech-Maranda, Constantine S Tam, Wojciech Jurczak, Koji Izutsu, Alvaro J Alencar, Manish R Patel, John F Seymour, Jennifer A Woyach, Philip A Thompson, Paolo B Abada, Caleb Ho, Samuel C McNeely, Narasimha Marella, Bastien Nguyen, Chunxiao Wang, Amy S Ruppert, Binoj Nair, Hui Liu, Donald E Tsai, Lindsey E Roeker, Paolo Ghia
<p><strong>Background: </strong>Richter transformation usually presents as an aggressive diffuse large B-cell lymphoma, occurs in up to 10% of patients with chronic lymphocytic leukaemia, has no approved therapies, and is associated with a poor prognosis. Pirtobrutinib has shown promising efficacy and tolerability in patients with relapsed or refractory B-cell malignancies, including those who progress on covalent Bruton tyrosine kinase (BTK) inhibitors. This study aims to report the safety and activity of pirtobrutinib monotherapy in a subgroup of patients with Richter transformation from the multicentre, open-label, phase 1/2 BRUIN study.</p><p><strong>Methods: </strong>This analysis included adult patients (aged ≥18 years) with histologically confirmed Richter transformation, an Eastern Cooperative Oncology Group performance status score of 0-2, and no limit of previous therapies, with patients receiving first-line treatment added in a protocol amendment (version 9.0, Dec 15, 2021). Pirtobrutinib 200 mg was administered orally once a day in 28-day cycles. The primary endpoint of phase 1 of the BRUIN trial as a whole, which has been previously reported, was to establish the recommended phase 2 dose for pirtobrutinib monotherapy and the phase 2 primary endpoint was overall response rate. Safety and activity were measured in all patients who received at least one dose of pirtobrutinib monotherapy. This BRUIN phase 1/2 trial was registered with ClinicalTrials.gov and is closed to enrolment (NCT03740529).</p><p><strong>Findings: </strong>Between Dec 26, 2019, and July 22, 2022, 82 patients were enrolled, of whom five were enrolled during phase 1 and 77 during phase 2. All but one patient received a starting dose of 200 mg pirtobrutinib once a day as the recommended phase 2 dose. The remaining patient received 150 mg pirtobrutinib once a day, which was not escalated to 200 mg. The median age of patients was 67 years (IQR 59-72). 55 (67%) of 82 patients were male and 27 (33%) were female. Most patients were White (65 [79%] of 82). 74 (90%) of 82 patients received at least one previous Richter transformation-directed therapy. Most patients (61 [74%] of 82) had received previous covalent BTK inhibitor therapy for chronic lymphocytic leukaemia or Richter transformation. The overall response rate was 50·0% (95% CI 38·7-61·3). 11 (13%) of 82 patients had a complete response and 30 (37%) of 82 patients had a partial response. Eight patients with ongoing response electively discontinued pirtobrutinib to undergo stem-cell transplantation. The most common grade 3 or worse adverse event was neutropenia (n=19). There were no treatment-related deaths.</p><p><strong>Interpretation: </strong>Pirtobrutinib shows promising safety and activity among patients with Richter transformation, most of whom received previous Richter transformation-directed therapy, including covalent BTK inhibitors. These data suggest that further investigation is warranted of pirtobrutinib
{"title":"Pirtobrutinib, a highly selective, non-covalent (reversible) BTK inhibitor in patients with B-cell malignancies: analysis of the Richter transformation subgroup from the multicentre, open-label, phase 1/2 BRUIN study.","authors":"William G Wierda, Nirav N Shah, Chan Y Cheah, David Lewis, Marc S Hoffmann, Catherine C Coombs, Nicole Lamanna, Shuo Ma, Deepa Jagadeesh, Talha Munir, Yucai Wang, Toby A Eyre, Joanna M Rhodes, Matthew McKinney, Ewa Lech-Maranda, Constantine S Tam, Wojciech Jurczak, Koji Izutsu, Alvaro J Alencar, Manish R Patel, John F Seymour, Jennifer A Woyach, Philip A Thompson, Paolo B Abada, Caleb Ho, Samuel C McNeely, Narasimha Marella, Bastien Nguyen, Chunxiao Wang, Amy S Ruppert, Binoj Nair, Hui Liu, Donald E Tsai, Lindsey E Roeker, Paolo Ghia","doi":"10.1016/S2352-3026(24)00172-8","DOIUrl":"10.1016/S2352-3026(24)00172-8","url":null,"abstract":"<p><strong>Background: </strong>Richter transformation usually presents as an aggressive diffuse large B-cell lymphoma, occurs in up to 10% of patients with chronic lymphocytic leukaemia, has no approved therapies, and is associated with a poor prognosis. Pirtobrutinib has shown promising efficacy and tolerability in patients with relapsed or refractory B-cell malignancies, including those who progress on covalent Bruton tyrosine kinase (BTK) inhibitors. This study aims to report the safety and activity of pirtobrutinib monotherapy in a subgroup of patients with Richter transformation from the multicentre, open-label, phase 1/2 BRUIN study.</p><p><strong>Methods: </strong>This analysis included adult patients (aged ≥18 years) with histologically confirmed Richter transformation, an Eastern Cooperative Oncology Group performance status score of 0-2, and no limit of previous therapies, with patients receiving first-line treatment added in a protocol amendment (version 9.0, Dec 15, 2021). Pirtobrutinib 200 mg was administered orally once a day in 28-day cycles. The primary endpoint of phase 1 of the BRUIN trial as a whole, which has been previously reported, was to establish the recommended phase 2 dose for pirtobrutinib monotherapy and the phase 2 primary endpoint was overall response rate. Safety and activity were measured in all patients who received at least one dose of pirtobrutinib monotherapy. This BRUIN phase 1/2 trial was registered with ClinicalTrials.gov and is closed to enrolment (NCT03740529).</p><p><strong>Findings: </strong>Between Dec 26, 2019, and July 22, 2022, 82 patients were enrolled, of whom five were enrolled during phase 1 and 77 during phase 2. All but one patient received a starting dose of 200 mg pirtobrutinib once a day as the recommended phase 2 dose. The remaining patient received 150 mg pirtobrutinib once a day, which was not escalated to 200 mg. The median age of patients was 67 years (IQR 59-72). 55 (67%) of 82 patients were male and 27 (33%) were female. Most patients were White (65 [79%] of 82). 74 (90%) of 82 patients received at least one previous Richter transformation-directed therapy. Most patients (61 [74%] of 82) had received previous covalent BTK inhibitor therapy for chronic lymphocytic leukaemia or Richter transformation. The overall response rate was 50·0% (95% CI 38·7-61·3). 11 (13%) of 82 patients had a complete response and 30 (37%) of 82 patients had a partial response. Eight patients with ongoing response electively discontinued pirtobrutinib to undergo stem-cell transplantation. The most common grade 3 or worse adverse event was neutropenia (n=19). There were no treatment-related deaths.</p><p><strong>Interpretation: </strong>Pirtobrutinib shows promising safety and activity among patients with Richter transformation, most of whom received previous Richter transformation-directed therapy, including covalent BTK inhibitors. These data suggest that further investigation is warranted of pirtobrutinib ","PeriodicalId":48726,"journal":{"name":"Lancet Haematology","volume":" ","pages":"e682-e692"},"PeriodicalIF":15.4,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141735433","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-01Epub Date: 2024-06-12DOI: 10.1016/S2352-3026(24)00167-4
Rafael S Cires-Drouet
{"title":"Anticoagulation in patients with inferior vena cava agenesia.","authors":"Rafael S Cires-Drouet","doi":"10.1016/S2352-3026(24)00167-4","DOIUrl":"10.1016/S2352-3026(24)00167-4","url":null,"abstract":"","PeriodicalId":48726,"journal":{"name":"Lancet Haematology","volume":" ","pages":"e555-e556"},"PeriodicalIF":15.4,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141327993","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-01DOI: 10.1016/S2352-3026(24)00217-5
Emma Wilkinson
{"title":"Aaron Goodman: \"people tell me they've been waiting for someone to speak up\".","authors":"Emma Wilkinson","doi":"10.1016/S2352-3026(24)00217-5","DOIUrl":"10.1016/S2352-3026(24)00217-5","url":null,"abstract":"","PeriodicalId":48726,"journal":{"name":"Lancet Haematology","volume":"11 8","pages":"e563"},"PeriodicalIF":15.4,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141876373","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-01Epub Date: 2024-07-02DOI: 10.1016/S2352-3026(24)00144-3
Bruno Fattizzo, Monia Marchetti, Marc Michel, Silvia Cantoni, Henrik Frederiksen, Giulio Giordano, Andreas Glenthøj, Tomás José González-López, Irina Murakhovskaya, Mariasanta Napolitano, Maria-Eva Mingot, Maria Arguello, Andrea Patriarca, Simona Raso, Nicola Vianelli, Wilma Barcellini
Evans syndrome is a rare disease marked by a severe clinical course, high relapse rate, infectious and thrombotic complications, and sometimes fatal outcome. Management is highly heterogeneous. There are several case reports but few large retrospective studies and no prospective or randomised trials. Here, we report the results of the first consensus-based expert recommendations aimed at harmonising the diagnosis and management of Evans syndrome in adults. After reviewing the literature, we used a fuzzy Delphi consensus method, with two rounds of a 42-item questionnaire that were scored by a panel of 13 international experts from five countries using a 7-point Likert scale. Panellists were selected by the core panel on the basis of their personal experience and previous publications on Evans syndrome and immune cytopenias; they met virtually throughout 2023. The panellists recommended extensive clinical and laboratory diagnostic tests, including bone marrow evaluation and CT scan, and an aggressive front-line therapy with prednisone (with or without intravenous immunoglobulins), with different treatment durations and tapering for immune thrombocytopenia and autoimmune haemolytic anaemias (AIHAs). Rituximab was strongly recommended as first-line treatment in cold-type AIHA and as second-line treatment in warm-type AIHA and patients with immune thrombocytopenia and antiphospholipid antibodies, previous thrombotic events, or associated lymphoproliferative diseases. However, rituximab was discouraged for patients with immunodeficiency or severe infections, with the same applying to splenectomy. Thrombopoietin receptor agonists were recommended for chronic immune thrombocytopenia and in the case of previous grade 4 infection. Fostamatinib was recommended as third-line or further-line treatment and suggested as second-line therapy for patients with previous thrombotic events. Immunosuppressive agents have been moved to third-line or further-line treatment. The panellists recommended the use of recombinant erythropoietin in AIHA in the case of inadequate reticulocyte counts, use of the complement inhibitor sutimlimab for relapsed cold AIHA, and the combination of rituximab plus bendamustine in Evans syndrome secondary to lymphoproliferative disorders. Finally, recommendations were given for supportive therapy, platelet or red blood cell transfusions, and thrombotic and antibiotic prophylaxis. These consensus-based recommendations should facilitate best practice for diagnosis and management of Evans syndrome in clinical practice.
{"title":"Diagnosis and management of Evans syndrome in adults: first consensus recommendations.","authors":"Bruno Fattizzo, Monia Marchetti, Marc Michel, Silvia Cantoni, Henrik Frederiksen, Giulio Giordano, Andreas Glenthøj, Tomás José González-López, Irina Murakhovskaya, Mariasanta Napolitano, Maria-Eva Mingot, Maria Arguello, Andrea Patriarca, Simona Raso, Nicola Vianelli, Wilma Barcellini","doi":"10.1016/S2352-3026(24)00144-3","DOIUrl":"10.1016/S2352-3026(24)00144-3","url":null,"abstract":"<p><p>Evans syndrome is a rare disease marked by a severe clinical course, high relapse rate, infectious and thrombotic complications, and sometimes fatal outcome. Management is highly heterogeneous. There are several case reports but few large retrospective studies and no prospective or randomised trials. Here, we report the results of the first consensus-based expert recommendations aimed at harmonising the diagnosis and management of Evans syndrome in adults. After reviewing the literature, we used a fuzzy Delphi consensus method, with two rounds of a 42-item questionnaire that were scored by a panel of 13 international experts from five countries using a 7-point Likert scale. Panellists were selected by the core panel on the basis of their personal experience and previous publications on Evans syndrome and immune cytopenias; they met virtually throughout 2023. The panellists recommended extensive clinical and laboratory diagnostic tests, including bone marrow evaluation and CT scan, and an aggressive front-line therapy with prednisone (with or without intravenous immunoglobulins), with different treatment durations and tapering for immune thrombocytopenia and autoimmune haemolytic anaemias (AIHAs). Rituximab was strongly recommended as first-line treatment in cold-type AIHA and as second-line treatment in warm-type AIHA and patients with immune thrombocytopenia and antiphospholipid antibodies, previous thrombotic events, or associated lymphoproliferative diseases. However, rituximab was discouraged for patients with immunodeficiency or severe infections, with the same applying to splenectomy. Thrombopoietin receptor agonists were recommended for chronic immune thrombocytopenia and in the case of previous grade 4 infection. Fostamatinib was recommended as third-line or further-line treatment and suggested as second-line therapy for patients with previous thrombotic events. Immunosuppressive agents have been moved to third-line or further-line treatment. The panellists recommended the use of recombinant erythropoietin in AIHA in the case of inadequate reticulocyte counts, use of the complement inhibitor sutimlimab for relapsed cold AIHA, and the combination of rituximab plus bendamustine in Evans syndrome secondary to lymphoproliferative disorders. Finally, recommendations were given for supportive therapy, platelet or red blood cell transfusions, and thrombotic and antibiotic prophylaxis. These consensus-based recommendations should facilitate best practice for diagnosis and management of Evans syndrome in clinical practice.</p>","PeriodicalId":48726,"journal":{"name":"Lancet Haematology","volume":" ","pages":"e617-e628"},"PeriodicalIF":15.4,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141538796","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-01Epub Date: 2024-06-12DOI: 10.1016/S2352-3026(24)00138-8
Carlos Bravo-Pérez, Ana Blanco, Nuria Revilla, Jorge Cobos, Alba Salgado-Parente, Susana Asenjo, Ramiro Méndez, Luis Marti-Bonmati, Santiago Bonanad, José C Albillos, Nerea Castro, Shally Marcellini, Paul López Sala, Maialen Lasa, José M Bastida, María S Infante, Miguel A Corral, Javier Pagan, Pilar Llamas, Juan J Rodríguez-Sevilla, Agustín Rodríguez-Alen, Teresa S Sevivas, Daniela Morello, Cristina García Villar, Sara Lojo, Ana Marco, Paolo Simioni, Vicente Vicente, María L Lozano, María E de la Morena-Barrio, José M García-Santos, Javier Corral
<p><strong>Background: </strong>Inferior vena cava agenesis (IVCA) is a rare anomaly predisposing affected people to lower-limb venous thrombosis with low frequency of pulmonary embolism. Antenatal thrombosis and inherited thrombophilia have been suggested as causes of IVCA. However, there is little evidence on the clinical course and management of this condition. We designed a patient registry to assess the thrombotic risk and features of IVCA.</p><p><strong>Methods: </strong>In this this multicentre, retrospective, observational study, we included patients with IVCA diagnosed by routine imaging from 20 hospitals in Spain (n=18), Portugal (n=1), and Italy (n=1). Patients were identified from a systematic search in radiology databases using data extraction software (cohort A) and alternative searches in medical records for confirmed IVCA (cohort B; option allowed when systematic approaches were unapplicable). Primary outcomes were clinical and imaging features, thrombotic risk, phenotype of IVCA-associated thrombosis, anticoagulant treatment, and the results of thrombophilia testing.</p><p><strong>Findings: </strong>We included patients with IVCA diagnosed by routine imaging studies done between Jan 1, 2010, and Dec 31, 2022. In the systematic search, 4 341 333 imaging exams were screened from the radiology databases of eight centres. 122 eligible patients were enrolled in cohort A. A further 95 patients were identified by screening medical records at 12 centres, of whom 88 were eligible and included in cohort B, making a combined cohort of 210 patients. 96 (46%) of 210 patients were female and 200 (95%) were European or Hispanic. 60 (29%) of 210 patients had hepatic IVC interruption, whereas 150 (71%) had extrahepatic IVCA. In cohort A, 65 (53%) of 122 patients had venous thrombosis, with an estimated annual risk of 1·15% (95% CI 0·89-1·46). Extrahepatic IVCA was associated with a greater risk of venous thrombosis than hepatic IVCA (56 [67%] of 84 patients vs nine [24%] of 38 patients, odds ratio 5·31, 95% CI 2·27-12·43; p<0·0001). Analysis of 126 patients with venous thrombosis pooled from cohorts A and B showed early-onset (median age 34·6 years, IQR 23·3-54·3) and recurrent events (50 [40%] of 126 patients). Patients with extrahepatic IVCA had greater proportions of lower-limb venous thrombosis (95 [87%] of 109 vs nine [53%] of 17, p=0·0010) and recurrence (48 [44%] of 109 vs two [12%] of 17, p=0·015), but lower rates of pulmonary embolism (10 [10%] of 99 vs four [33%] of 12, p=0·044) than did patients with hepatic IVCA. 77 (63%) of 122 patients with thrombosis underwent indefinite anticoagulation. 32 (29%) of 111 patients (29 [34%] of 86 with thrombosis) had coexisting thrombophilias. The recurrence risk was lower for patients receiving indefinite anticoagulation (adjusted odds ratio 0·24, 95% CI 0·08-0·61; p=0·010), and greater for thrombophilias (3·19, 1·09-9·32; p=0·034).</p><p><strong>Interpretation: </strong>This evaluation of a large p
{"title":"Thrombotic risk and features of patients with inferior vena cava agenesis: a multicentre, retrospective, observational study.","authors":"Carlos Bravo-Pérez, Ana Blanco, Nuria Revilla, Jorge Cobos, Alba Salgado-Parente, Susana Asenjo, Ramiro Méndez, Luis Marti-Bonmati, Santiago Bonanad, José C Albillos, Nerea Castro, Shally Marcellini, Paul López Sala, Maialen Lasa, José M Bastida, María S Infante, Miguel A Corral, Javier Pagan, Pilar Llamas, Juan J Rodríguez-Sevilla, Agustín Rodríguez-Alen, Teresa S Sevivas, Daniela Morello, Cristina García Villar, Sara Lojo, Ana Marco, Paolo Simioni, Vicente Vicente, María L Lozano, María E de la Morena-Barrio, José M García-Santos, Javier Corral","doi":"10.1016/S2352-3026(24)00138-8","DOIUrl":"10.1016/S2352-3026(24)00138-8","url":null,"abstract":"<p><strong>Background: </strong>Inferior vena cava agenesis (IVCA) is a rare anomaly predisposing affected people to lower-limb venous thrombosis with low frequency of pulmonary embolism. Antenatal thrombosis and inherited thrombophilia have been suggested as causes of IVCA. However, there is little evidence on the clinical course and management of this condition. We designed a patient registry to assess the thrombotic risk and features of IVCA.</p><p><strong>Methods: </strong>In this this multicentre, retrospective, observational study, we included patients with IVCA diagnosed by routine imaging from 20 hospitals in Spain (n=18), Portugal (n=1), and Italy (n=1). Patients were identified from a systematic search in radiology databases using data extraction software (cohort A) and alternative searches in medical records for confirmed IVCA (cohort B; option allowed when systematic approaches were unapplicable). Primary outcomes were clinical and imaging features, thrombotic risk, phenotype of IVCA-associated thrombosis, anticoagulant treatment, and the results of thrombophilia testing.</p><p><strong>Findings: </strong>We included patients with IVCA diagnosed by routine imaging studies done between Jan 1, 2010, and Dec 31, 2022. In the systematic search, 4 341 333 imaging exams were screened from the radiology databases of eight centres. 122 eligible patients were enrolled in cohort A. A further 95 patients were identified by screening medical records at 12 centres, of whom 88 were eligible and included in cohort B, making a combined cohort of 210 patients. 96 (46%) of 210 patients were female and 200 (95%) were European or Hispanic. 60 (29%) of 210 patients had hepatic IVC interruption, whereas 150 (71%) had extrahepatic IVCA. In cohort A, 65 (53%) of 122 patients had venous thrombosis, with an estimated annual risk of 1·15% (95% CI 0·89-1·46). Extrahepatic IVCA was associated with a greater risk of venous thrombosis than hepatic IVCA (56 [67%] of 84 patients vs nine [24%] of 38 patients, odds ratio 5·31, 95% CI 2·27-12·43; p<0·0001). Analysis of 126 patients with venous thrombosis pooled from cohorts A and B showed early-onset (median age 34·6 years, IQR 23·3-54·3) and recurrent events (50 [40%] of 126 patients). Patients with extrahepatic IVCA had greater proportions of lower-limb venous thrombosis (95 [87%] of 109 vs nine [53%] of 17, p=0·0010) and recurrence (48 [44%] of 109 vs two [12%] of 17, p=0·015), but lower rates of pulmonary embolism (10 [10%] of 99 vs four [33%] of 12, p=0·044) than did patients with hepatic IVCA. 77 (63%) of 122 patients with thrombosis underwent indefinite anticoagulation. 32 (29%) of 111 patients (29 [34%] of 86 with thrombosis) had coexisting thrombophilias. The recurrence risk was lower for patients receiving indefinite anticoagulation (adjusted odds ratio 0·24, 95% CI 0·08-0·61; p=0·010), and greater for thrombophilias (3·19, 1·09-9·32; p=0·034).</p><p><strong>Interpretation: </strong>This evaluation of a large p","PeriodicalId":48726,"journal":{"name":"Lancet Haematology","volume":" ","pages":"e606-e616"},"PeriodicalIF":15.4,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141327994","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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