학술논문
Intention-to-treat outcomes utilising a stringent event definition in children and young people treated with tisagenlecleucel for r/r ALL through a national access scheme.
Document Type
Academic Journal
Author
Oporto Espuelas M; Infection, Immunity and Inflammation, UCL Great Ormond Ormond Street Institute of Child Health, London, UK. m.oporto@ucl.ac.uk.; Burridge S; Department of Haematology, Great Ormond Street Hospital, London, UK.; Kirkwood AA; Cancer Research UK & Cancer Trials Centre, UCL, London, UK.; Bonney D; Department of Blood and Bone Marrow Transplant, Royal Manchester Children's Hospital, Manchester, UK.; Watts K; Department of Blood and Bone Marrow Transplant, Royal Manchester Children's Hospital, Manchester, UK.; Shenton G; Great North Children's Hospital, Newcastle upon Tyne, UK.; Jalowiec KA; Department of Haematology, University College London Hospitals NHS Foundation Trust, London, UK.; O'Reilly MA; Department of Haematology, University College London Hospitals NHS Foundation Trust, London, UK.; Roddie C; Department of Haematology, University College London Hospitals NHS Foundation Trust, London, UK.; Castleton A; Department of Haematology, The Christie Hospital NHS Foundation Trust, Manchester, UK.; Clesham K; Department of Haematology, University College London Hospitals NHS Foundation Trust, London, UK.; Nicholson E; Department of Haematology/Bone Marrow Transplantation, The Royal Marsden NHS Foundation Trust, London, UK.; Institute of Cancer Research, London, UK.; Alajangi R; Department of Haematology/Bone Marrow Transplant, University Hospitals Bristol and Weston NHS Foundation Trust, Bristol, UK.; Prabhu S; Department of Haematology/Bone Marrow Transplant, University Hospitals Bristol and Weston NHS Foundation Trust, Bristol, UK.; George L; Centre for Clinical Haematology, Queen Elizabeth Hospital, Birmingham, UK.; Uttenthal B; Cambridge University Hospital NHS Foundation Trust, Cambridge, UK.; Gabelli M; Department of Bone Marrow Transplant, Great Ormond Street Hospital, London, UK.; Pediatric Onco-hematology and Hematopoietic Stem Cell Transplantation, Woman and Child Health Department, University of Padova, Padua, Italy.; Neill L; Department of Haematology, University College London Hospitals NHS Foundation Trust, London, UK.; Besley C; Department of Haematology/Bone Marrow Transplant, University Hospitals Bristol and Weston NHS Foundation Trust, Bristol, UK.; Chaganti S; Centre for Clinical Haematology, Queen Elizabeth Hospital, Birmingham, UK.; Wynn RF; Department of Blood and Bone Marrow Transplant, Royal Manchester Children's Hospital, Manchester, UK.; Bartram J; Department of Haematology, Great Ormond Street Hospital, London, UK.; Chiesa R; Department of Bone Marrow Transplant, Great Ormond Street Hospital, London, UK.; Lucchini G; Department of Bone Marrow Transplant, Great Ormond Street Hospital, London, UK.; Pavasovic V; Department of Haematology, Great Ormond Street Hospital, London, UK.; Rao A; Department of Haematology, Great Ormond Street Hospital, London, UK.; Rao K; Department of Bone Marrow Transplant, Great Ormond Street Hospital, London, UK.; Silva J; Department of Bone Marrow Transplant, Great Ormond Street Hospital, London, UK.; Samarasinghe S; Department of Haematology, Great Ormond Street Hospital, London, UK.; Vora A; Department of Haematology, Great Ormond Street Hospital, London, UK.; Clark P; NHS England, London, UK.; Cummins M; Bristol Royal Hospital for Children, Bristol, UK.; Marks DI; Department of Haematology, University Hospitals Bristol, Bristol, UK.; Amrolia P; Infection, Immunity and Inflammation, UCL Great Ormond Ormond Street Institute of Child Health, London, UK.; Department of Bone Marrow Transplant, Great Ormond Street Hospital, London, UK.; Hough R; Department of Haematology, University College London Hospitals NHS Foundation Trust, London, UK.; Ghorashian S; Department of Haematology, Great Ormond Street Hospital, London, UK.; Developmental Biology and Cancer, UCL Great Ormond Ormond Street Institute of Child Health, London, UK.
Source
Publisher: Nature Pub. Group Country of Publication: United States NLM ID: 101568469 Publication Model: Electronic Cited Medium: Internet ISSN: 2044-5385 (Electronic) Linking ISSN: 20445385 NLM ISO Abbreviation: Blood Cancer J Subsets: MEDLINE
Subject
Language
English
Abstract
CAR T-cell therapy has transformed relapsed/refractory (r/r) B-cell precursor acute lymphoblastic leukaemia (B-ALL) management and outcomes, but following CAR T infusion, interventions are often needed. In a UK multicentre study, we retrospectively evaluated tisagenlecleucel outcomes in all eligible patients, analysing overall survival (OS) and event-free survival (EFS) with standard and stringent definitions, the latter including measurable residual disease (MRD) emergence and further anti-leukaemic therapy. Both intention-to-treat and infused cohorts were considered. We collected data on feasibility of delivery, manufacture, toxicity, cause of therapy failure and followed patients until death from any cause. Of 142 eligible patients, 125 received tisagenlecleucel, 115/125 (92%) achieved complete remission (CR/CRi). Severe cytokine release syndrome and neurotoxicity occurred in 16/123 (13%) and 10/123 (8.1%), procedural mortality was 3/126 (2.4%). The 2-year intent to treat OS and EFS were 65.2% (95%CI 57.2-74.2%) and 46.5% (95%CI 37.6-57.6%), 2-year intent to treat stringent EFS was 35.6% (95%CI 28.1-44.9%). Median OS was not reached. Sixty-two responding patients experienced CAR T failure by the stringent event definition. Post failure, 1-year OS and standard EFS were 61.2% (95%CI 49.3-75.8) and 55.3% (95%CI 43.6-70.2). Investigation of CAR T-cell therapy for B-ALL delivered on a country-wide basis, including following patients beyond therapy failure, provides clinicians with robust outcome measures. Previously, outcomes post CAR T-cell therapy failure were under-reported. Our data show that patients can be successfully salvaged in this context with good short-term survival.
(© 2024. The Author(s).)
(© 2024. The Author(s).)