An updated UK real-world analysis of factors affecting outcome following brexucabtagene autoleucel for relapsed or refractory adult acute lymphoblastic leukemia
Year: 2025
Type: conference-abstract
Abstract: Background The UK Adult ALL CAR-T panel - established May 2023 - promotes equity of access and consistent eligibility assessment for nationally commissioned CAR-T therapies. This collaborative platform supports robust collection and assessment of real-world data (RWD). We previously reported RWD around use, toxicity and outcomes of adult ALL patients (pts) approved for brexu-cel therapy in the 1st 12mo of nationally funded access. Here we provide an updated analysis of UK CAR-T use for adult ALL and evaluate factors influencing outcome following brexu-cel infusion. Methods All pts approved for brexu-cel by panel between May 2023-April 2025 and with sufficient data were included. Retrospective data from 20 accredited immune effector cell centres were anonymised, collected on a standardised proforma and collated to support RWD analysis. Results Of 134 pts assessed, 92 were eligible for brexu-cel by national criteria (ITT cohort). Indications were post-allo-SCT relapse (60; 65.2%); 1st relapse within 12mo of CR1 (11; 12.0%); 2nd/subsequent relapse (7; 7.6%); relapse in non-SCT candidate (4; 4.4%); refractory disease (10; 10.8%). Median age (ITT) was 50.5y (IQR 40.5-59y), with 21 (22.8%) >60y. One-third (30; 33.3%) had tyrosine kinase activating fusions; 17 (18.9%) and 7 (7.8%) had v high and high-risk cytogenetics, respectively (per revised UKALL14 genetic risk). Median prior therapy lines were 2 (1-5), including prior allo-SCT, blinatumomab and inotuzumab in 61 (66.3%), 26 (28.3%) and 21 (22.8%), respectively. Of approved cases, 83 (88%) underwent apheresis (2 failed apheresis; 1 failed manufacture). Ultimately, 68 (73.9% of approved; 85% with product) underwent brexu-cel infusion. Median time from approval to infusion was 57.5d (IQR 43.5-74.5); 95.6% received bridging (84.6% 1 line only). At infusion 48 (73.8%) were in CR, with 53 (77.9%) having BM blasts <5% and 16 (24.6%) confirmed MRD negative. At D30 and D90 post-infusion, 58 (95.1%) and 49 (98%) were in CR, with 52 (85.2%) and 41 (82%) MRD negative, respectively. Of responders, 79% (95% CI 65.1-87.9) maintained response at 6mo. Five (7.4%) went on to allo-SCT. Grade 3+ CRS and ICANS occurred in 2.9% and 23.5% of cases, respectively. With median 12mo FU [95% CI 6.7-14.5] from infusion, 6mo relapse-free (RFS) and overall survival (OS) was 73.9% and 85.5%, respectively. Estimated median RFS was 17.1mo (95% CI 9.9-NR); median OS was not reached. Disease burden at infusion predicted outcome, with est median RFS for pts with ≤5% and >5% blasts of 20.1mo [95% CI 13.5-NR] and 4.2mo [95% CI 0.0-9.9] respectively (log-rank p<0.001). MRD-negativity at infusion was associated with improved RFS (median NR v 11.7mo [95% CI 7.3-20.0]; est 12mo RFS 90.0% [95% CI 47.3-98.5] v 50.0% [95% CI 33.6-64.3]; log-rank p=0.014). Prior EMD predicted worse RFS (median 4.7mo [95% CI 0-13.5] v 19.2mo [95% CI 11.3-NR]; log-rank p=0.004) and OS (median 9.0mo [95% 0.9-NR] v NR; log-rank p=0.021). Prior blinatumomab was associated with worse RFS (median 11.3mo [95% CI 3.3-NR] v 19.2mo [95% CI 9.9-NR]; log-rank p=0.046) and OS (median 14.2mo [95% CI 3.6-NR] v NR; log-rank p=0.042). OS was not impacted by prior inotuzumab exposure (any ino p=0.375; ino as bridging p=0.573). Relapse within 6mo of prior allo-SCT predicted poor outcomes post CAR-T (v relapse ≥6mo post-SCT: RFS p<0.001; OS p=0.015). In univariate Cox regression models, prior EMD (RFS HR 3.18 [1.38–7.33]; OS HR 3.22 [1.13–9.21]), >5% blasts (RFS HR 5.17 [2.35–11.39]; OS HR 4.04 [1.55–10.54]), and post-SCT relapse within 6mo (RFS HR 6.51 [2.16-19.63]; OS HR 4.70 [1.20-18.41]) predicted inferior outcomes. Adjusted for age, all retained significance (EMD: RFS HR 3.21 [1.39–7.43]; OS HR 3.04 [1.05–8.79]; >5% blasts: RFS HR 5.31 [2.39–11.82]; OS HR 4.30 [1.63–11.47]; post-SCT relapse <6mo: RFS HR 6.53 [2.12-20.08]; OS HR 4.50 [1.07-18.93]). Conclusion Here we present one of the largest RWD analyses of brexu-cel use in adult ALL. Brexu-cel was deliverable, tolerable, and efficacious, in a cohort notably differing from that trialled in ZUMA-3, including a higher proportion post-SCT, older median age, and more in CR at infusion. Outcomes were strongly influenced by disease burden at infusion and EMD status: the latter may be relevant in the frontline blinatumomab era (in which patterns of relapse may differ). Early post-SCT relapse (<6mo) was also associated with worse CAR-T outcomes, highlighting need for risk-adapted strategies in this subgroup.
Source: Blood
Authors: Anna Castleton, Michelle Lannon, Ned Atiyah, Alexandra Smith, Ahmed Abdulgawad, Mariam Amer, Farhan Anjum, Kathleen Cheok, David Burns, Richard Burt, Sridhar Chaganti, Johannes De Vos, Gerardo Errico, Adele Fielding, Lindsay George, Katharine Hodby, David Irvine, Shenbagaram Kasivisvanathan, Philippa Kelsey, Katja Kimberger, Andrew King, Anne-Louise Latif, David Marks, Navta Masand, Pierre McCarthy, Tobias Menne, Anthony Moorman, Nick Morley, Emma Nicholson, Maeve O'Reilly, Deborah Richardson, Huw Roddie, Clare Rowntree, Muhammad Saif, Thomas Seddon, Belen Sevillano, Kirsty Sharplin, Eleni Tholouli, Bela Patel Wrench, Deborah Yallop
Institutions: The Christie Hospital, The Christie NHS Foundation Trust, University of York, University Hospital Southampton NHS Foundation Trust, Manchester Royal Infirmary, University Hospitals Plymouth NHS Trust, University College London, Barts Health NHS Trust, Nottingham University Hospitals NHS Trust, Queen Elizabeth University Hospital, Cambridge University Hospitals NHS Foundation Trust, Sheffield Teaching Hospitals NHS Foundation Trust, Leeds Teaching Hospitals NHS Trust, University of Bristol, Newcastle University, Royal Marsden Hospital, Western General Hospital, University Hospital of Wales, Clatterbridge Cancer Centre NHS Foundation Trust, St George's Hospital, Oxford University Hospitals NHS Trust, Barts Cancer Institute, King's College Hospital NHS Foundation Trust
Language: English
Topic: CAR-T cell therapy research
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W4417011801
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