4 research outputs found
Brexucabtagene autoleucel for relapsed or refractory mantle cell lymphoma in the United Kingdom: A realâworld intentionâtoâtreat analysis
Brexucabtagene autoleucel (brexuâcel) is an autologous CD19 CAR Tâcell product, approved for relapsed/refractory (r/r) mantle cell lymphoma (MCL). In ZUMAâ2, brexuâcel demonstrated impressive responses in patients failing â„2 lines, including a bruton's tyrosine kinase inhibitor, with an overall and complete response rate of 93% and 67%, respectively. Here, we report our realâworld intentionâtoâtreat (ITT) outcomes for brexuâcel in consecutive, prospectively approved patients, from 12 institutions in the United Kingdom between February 2021 and June 2023, with a focus on feasibility, efficacy, and tolerability. Of 119 approved, 104 underwent leukapheresis and 83 received a brexuâcel infusion. Progressive disease (PD) and/or manufacturing (MF) were the most common reasons for failure to reach harvest and/or infusion. For infused patients, best overall and complete response rates were 87% and 81%, respectively. At a median followâup of 13.3 months, median progressionâfree survival (PFS) for infused patients was 21 months (10.1âNA) with a 6â and 12âmonth PFS of 82% (95% confidence interval [CI], 71â89) and 62% (95% CI, 49â73), respectively. â„Grade 3 cytokine release syndrome and neurotoxicity occurred in 12% and 22%, respectively. On multivariate analysis, inferior PFS was associated with male sex, bulky disease, ECOG PS > 1 and previous MF. Cumulative incidence of nonârelapse mortality (NRM) was 6%, 15%, and 25% at 6, 12, and 24 months, respectively, and mostly attributable to infection. Outcomes for infused patients in the UK are comparable to ZUMAâ2 and other realâworld reports. However, ITT analysis highlights a significant dropout due to PD and/or MF. NRM events warrant further attention
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Brexucabtagene autoleucel for relapsed or refractory mantle cell lymphoma in the United Kingdom: A realâworld intentionâtoâtreat analysis
Publication status: PublishedAbstractBrexucabtagene autoleucel (brexuâcel) is an autologous CD19 CAR Tâcell product, approved for relapsed/refractory (r/r) mantle cell lymphoma (MCL). In ZUMAâ2, brexuâcel demonstrated impressive responses in patients failing â„2 lines, including a bruton's tyrosine kinase inhibitor, with an overall and complete response rate of 93% and 67%, respectively. Here, we report our realâworld intentionâtoâtreat (ITT) outcomes for brexuâcel in consecutive, prospectively approved patients, from 12 institutions in the United Kingdom between February 2021 and June 2023, with a focus on feasibility, efficacy, and tolerability. Of 119 approved, 104 underwent leukapheresis and 83 received a brexuâcel infusion. Progressive disease (PD) and/or manufacturing (MF) were the most common reasons for failure to reach harvest and/or infusion. For infused patients, best overall and complete response rates were 87% and 81%, respectively. At a median followâup of 13.3 months, median progressionâfree survival (PFS) for infused patients was 21 months (10.1âNA) with a 6â and 12âmonth PFS of 82% (95% confidence interval [CI], 71â89) and 62% (95% CI, 49â73), respectively. â„Grade 3 cytokine release syndrome and neurotoxicity occurred in 12% and 22%, respectively. On multivariate analysis, inferior PFS was associated with male sex, bulky disease, ECOG PSâ>â1 and previous MF. Cumulative incidence of nonârelapse mortality (NRM) was 6%, 15%, and 25% at 6, 12, and 24 months, respectively, and mostly attributable to infection. Outcomes for infused patients in the UK are comparable to ZUMAâ2 and other realâworld reports. However, ITT analysis highlights a significant dropout due to PD and/or MF. NRM events warrant further attention.</jats:p
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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
Acknowledgements: Although this project received no specific funding, MOE is funded by Children with Cancer UK (CPTSTSFA\100003) and would like to acknowledge their support. We would like to thank all staff who have contributed to patientsâ care and especially acknowledge the late Amit Patel for his commitment to haematology and cell therapy. In addition, we would like to acknowledge all patients and their families.AbstractCAR 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 57.2â74.2%) and 46.5% (95%CI 37.6â57.6%), 2-year intent to treat stringent EFS was 35.6% (95%CI 28.1â44.9%). 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 49.3â75.8) and 55.3% (95%CI 43.6â70.2). 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.</jats:p