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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
Oporto Espuelas, M. Burridge, S. Kirkwood, A. A. Bonney, D. Watts, K. Shenton, G. Jalowiec, K. A. O'Reilly, M. A. Roddie, C. Castleton, Anna
Oporto Espuelas, M.
Burridge, S.
Kirkwood, A. A.
Bonney, D.
Watts, K.
Shenton, G.
Jalowiec, K. A.
O'Reilly, M. A.
Roddie, C.
Castleton, Anna
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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.
Authors
Oporto Espuelas, M.
Burridge, S.
Kirkwood, A. A.
Bonney, D.
Watts, K.
Shenton, G.
Jalowiec, K. A.
O'Reilly, M. A.
Roddie, C.
Castleton, Anna
Clesham, K.
Nicholson, E.
Alajangi, R.
Prabhu, S.
George, L.
Uttenthal, B.
Gabelli, M.
Neill, L.
Besley, C.
Chaganti, S.
Wynn, R. F.
Bartram, J.
Chiesa, R.
Lucchini, G.
Pavasovic, V.
Rao, A.
Rao, K.
Silva, J.
Samarasinghe, S.
Vora, A.
Clark, P.
Cummins, M.
Marks, D. I.
Amrolia, P.
Hough, R.
Ghorashian, S.
Burridge, S.
Kirkwood, A. A.
Bonney, D.
Watts, K.
Shenton, G.
Jalowiec, K. A.
O'Reilly, M. A.
Roddie, C.
Castleton, Anna
Clesham, K.
Nicholson, E.
Alajangi, R.
Prabhu, S.
George, L.
Uttenthal, B.
Gabelli, M.
Neill, L.
Besley, C.
Chaganti, S.
Wynn, R. F.
Bartram, J.
Chiesa, R.
Lucchini, G.
Pavasovic, V.
Rao, A.
Rao, K.
Silva, J.
Samarasinghe, S.
Vora, A.
Clark, P.
Cummins, M.
Marks, D. I.
Amrolia, P.
Hough, R.
Ghorashian, S.
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Date
2024
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Article
Citation
Oporto Espuelas M, Burridge S, Kirkwood AA, Bonney D, Watts K, Shenton G, et al. 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. Blood Cancer J. 2024 Apr 15;14(1):66. PubMed PMID: 38622139. Pubmed Central PMCID: PMC11018620 honoraria/support to attend conferences from Novartis. CR is on advisory board and receives honoraria from Novartis. AC receives consulting fees from Novartis. EN is on advisory board and has received support to attend conferences from Novartis. The rest of authors have no competing interests in relation to this work. Epub 2024/04/16. eng.