학술논문
Ibrutinib as part of risk-stratified treatment for posttransplant lymphoproliferative disorder: the phase 2 TIDaL trial.
Document Type
Academic Journal
Author
Chaganti S; Centre for Clinical Haematology, University Hospitals Birmingham National Health System Foundation Trust, Birmingham, United Kingdom.; Maycock S; Cancer Research UK Clinical Trials Unit, Institute of Cancer and Genomics Cancer, University of Birmingham, Birmingham, United Kingdom.; McIlroy G; Cancer Research UK Clinical Trials Unit, Institute of Cancer and Genomics Cancer, University of Birmingham, Birmingham, United Kingdom.; Jackson A; Cancer Research UK Clinical Trials Unit, Institute of Cancer and Genomics Cancer, University of Birmingham, Birmingham, United Kingdom.; Bishop R; Cancer Research UK Clinical Trials Unit, Institute of Cancer and Genomics Cancer, University of Birmingham, Birmingham, United Kingdom.; Johnson S; Cancer Research UK Clinical Trials Unit, Institute of Cancer and Genomics Cancer, University of Birmingham, Birmingham, United Kingdom.; Kanfer E; Department of Haematology, Hammersmith Hospital, Imperial College Healthcare National Health System Trust, London, United Kingdom.; Kassam S; Department of Haematology, King's College Hospital, King's College Hospital National Health System Foundation Trust, London, United Kingdom.; Cwynarski K; Department of Haematology, University College London Hospital, University College London Hospitals National Health System Foundation Trust, London, United Kingdom.; Wrench D; Department of Haematology, Guy's Hospital, Guy's and St Thomas' National Health System Foundation Trust, London, United Kingdom.; Arumainathan A; Department of Haematology, Clatterbridge Cancer Centre, The Clatterbridge Cancer Centre National Health System Foundation Trust, Liverpool, United Kingdom.; Fox CP; School of Medicine, University of Nottingham, Nottingham, United Kingdom.; Johnson R; Department of Clinical Haematology, St James's University Hospital, Leeds Teaching Hospitals National Health System Trust, Leeds, United Kingdom.; McKay P; Department of Haemato-oncology, Beatson West of Scotland Cancer Centre, National Health System Greater Glasgow and Clyde, Glasgow, Scotland.; Paneesha S; Centre for Clinical Haematology, University Hospitals Birmingham National Health System Foundation Trust, Birmingham, United Kingdom.; Rowntree C; Department of Haematology, University Hospital of Wales, Cardiff and Vale University Health Board, Cardiff, United Kingdom.; Balotis C; Clinical Haematology Service, Leicester Royal Infirmary, University Hospitals of Leicester National Health System Trust, Leicester, United Kingdom.; Collins GP; Department of Haematology, Oxford Cancer and Hematology Centre, Churchill Hospital, Oxford University Hospitals National Health System Foundation Trust, Oxford, United Kingdom.; Davies A; Department of Haematology, Southampton General Hospital, University Hospital Southampton National Health System Foundation Trust, Southampton, United Kingdom.; Wright J; Clinical Haematology Service, Royal Hallamshire Hospital, Sheffield Teaching Hospitals National Health System Foundation Trust, Sheffield, United Kingdom.; Burns S; Department of Haematology, Manchester Royal Infirmary, Manchester University National Health System Foundation Trust, Manchester, United Kingdom.; Laurence A; Department of Haematology, University College London Hospital, University College London Hospitals National Health System Foundation Trust, London, United Kingdom.; Wheatley K; Cancer Research UK Clinical Trials Unit, Institute of Cancer and Genomics Cancer, University of Birmingham, Birmingham, United Kingdom.; Menne T; Northern Centre for Cancer Care, Freeman Hospital, Newcastle upon Tyne Hospitals National Health System Foundation Trust, Newcastle upon Tyne, United Kingdom.
Source
Publisher: Elsevier Country of Publication: United States NLM ID: 7603509 Publication Model: Print Cited Medium: Internet ISSN: 1528-0020 (Electronic) Linking ISSN: 00064971 NLM ISO Abbreviation: Blood Subsets: MEDLINE
Subject
Language
English
Abstract
Abstract: Posttransplant lymphoproliferative disorder (PTLD) is a rare complication of solid organ transplantation, and cytotoxic chemotherapy is associated with treatment-related morbidity and mortality. Current treatment takes a sequential, risk-stratified approach, and patients with low-risk disease after initial immunotherapy can avoid escalation to immunochemotherapy. TIDaL is a prospective, single-arm phase 2 trial investigating the activity and tolerability of ibrutinib combined with risk-stratified therapy for first-line treatment of PTLD. Eligible patients were adults with newly diagnosed CD20+ B-cell PTLD after solid organ transplant and performance status 0 to 2. Initial treatment comprised 49 days of ibrutinib 560 mg once daily, with 4 doses of weekly rituximab. Treatment response on interim scan and baseline International Prognostic Index were used to allocate patients to either a low-risk arm (who continued ibrutinib, alongside 4 further doses of 3-weekly rituximab) or high-risk (escalation to rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone [R-CHOP] immunochemotherapy, with ibrutinib continuing in patients aged <65 years). The primary outcome was complete response on interim scan, achieved by 11 of 38 patients (29%; 95% confidence interval [CI], 15-46). This did not reach the prespecified threshold for clinically significant activity. Secondary outcomes included allocation to the low-risk arm (41% of patients), 2-year progression-free survival (58%; 95% CI, 44-76), and 2-year overall survival (76%; 95% CI, 63-91). Adverse events were mostly hematological, gastrointestinal, and infective. Although TIDaL does not support adding ibrutinib into first-line treatment of PTLD, increasing the proportion of patients who can be treated without cytotoxic chemotherapy remains an important aim of future research. This trial was registered at www.clinicaltrials.gov as #ISRCTN32667607.
(© 2024 American Society of Hematology. Published by Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.)
(© 2024 American Society of Hematology. Published by Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.)