The purpose of this study is to describe feasibility of delivering point-of-care manufactured CD19-directed CAR T-cell therapy to patients with relapsed/ refractory B-lineage leukaemia/ lymphoma.

开始日期2022-03-15

申办/合作机构

KK Women's & Children's Hospital Pte Ltd.

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100 项与 Anti-CD19 CAR T-cells(KK Women's and Children's Hospital) 相关的临床结果

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100 项与 Anti-CD19 CAR T-cells(KK Women's and Children's Hospital) 相关的转化医学

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100 项与 Anti-CD19 CAR T-cells(KK Women's and Children's Hospital) 相关的专利（医药）

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129

项与 Anti-CD19 CAR T-cells(KK Women's and Children's Hospital) 相关的文献（医药）

2024-12-31·Annals of Medicine

Comprehensive analysis of the efficacy and safety of CAR T-cell therapy in patients with relapsed or refractory B-cell acute lymphoblastic leukaemia: a systematic review and meta-analysis

Review

作者: Tuekprakhon, Aekkachai ; Alimsjah, Yohanes Audric ; Pawestri, Aulia Rahmi ; Tanjaya, Krisanto ; Willyanto, Sebastian Emmanuel

BACKGROUNDRelapse/refractory B-cell acute lymphoblastic leukaemia (r/r B-ALL) represents paediatric cancer with a challenging prognosis. CAR T-cell treatment, considered an advanced treatment, remains controversial due to high relapse rates and adverse events. This study assessed the efficacy and safety of CAR T-cell therapy for r/r B-ALL.METHODSThe literature search was performed on four databases. Efficacy parameters included minimal residual disease negative complete remission (MRD-CR) and relapse rate (RR). Safety parameters constituted cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS).RESULTSAnti-CD22 showed superior efficacy with the highest MRD-CR event rate and lowest RR, compared to anti-CD19. Combining CAR T-cell therapy with haploidentical stem cell transplantation improved RR. Safety-wise, bispecific anti-CD19/22 had the lowest CRS rate, and anti-CD22 showed the fewest ICANS. Analysis of the costimulatory receptors showed that adding CD28ζ to anti-CD19 CAR T-cell demonstrated superior efficacy in reducing relapses with favorable safety profiles.CONCLUSIONChoosing a more efficacious and safer CAR T-cell treatment is crucial for improving overall survival in acute leukaemia. Beyond the promising anti-CD22 CAR T-cell, exploring costimulatory domains and new CD targets could enhance treatment effectiveness for r/r B-ALL.

2024-12-01·American Journal of Hematology

Clinical outcomes and microenvironment profiling in relapsed/refractory multiple myeloma patients with extramedullary disease receiving anti‐BCMA CAR T‐cell‐based therapy

Article

作者: Sang, Wei ; Li, Hujun ; Cheng, Hai ; Gu, Weiying ; Li, Zhenyu ; Zheng, Junnian ; Yan, Zhiling ; Chen, Wei ; Qiao, Jianlin ; Qiu, Tingting ; Xu, Kailin ; Qi, Yuekun ; Cao, Jiang ; Zhu, Feng ; Wang, Gang ; Fei, Xiaoming ; Shi, Ming ; Qi, Kunming ; Pan, Bin ; Li, Depeng ; Miao, Yuqing ; Wang, Ying ; Huang, Hongming

AbstractRelapsed/refractory multiple myeloma patients with extramedullary disease (EMD) have unfavorable prognosis and lack effective therapy. Chimeric antigen receptor (CAR) T‐cell activities in EMD have yet to be determined; how EMD‐specific microenvironment influences the clinical outcomes of CAR T‐cell therapy remains of great interest. In this prospective cohort study, patients with histologically confirmed extra‐osseous EMD were enrolled and treated with combined anti‐BCMA and anti‐CD19 CAR T‐cell therapy from May 2017 to September 2023. Thirty‐one patients were included in the study. Overall response occurred in 90.3% of medullary disease and 64.5% of EMD (p = .031). Discrepancies in treatment response were noted between medullary and extramedullary diseases, with EMD exhibiting suboptimal and delayed response, as well as shortened response duration. With a median follow‐up of 25.3 months, the median progression‐free and overall survival were 5.0 and 9.7 months, respectively. Landmark analysis demonstrated that progression within 6 months post‐infusion is strongly associated with an increased risk of death (HR = 4.58; p = .029). Compared with non‐EMD patients, patients with EMD showed inferior survival outcomes. Unique CAR‐associated local toxicities at EMD were seen in 22.6% patients and correlated with the occurrence and severity of systemic cytokine release syndrome. To the cutoff date, 65% treated patients experienced EMD progression, primarily in the form of BCMA+ progression. The pretherapy EMD immunosuppressive microenvironment, characterized by infiltration of exhausted CD8+ T cells, was associated with inferior clinical outcomes. CAR T cells have therapeutic activity in relapsed/refractory EMD, but the long‐term survival benefits may be limited. EMD‐specific microenvironment potentially impacts treatment. Further efforts are needed to extend EMD remission and improve long‐term outcomes.

2024-11-01·Clinical Lymphoma Myeloma and Leukemia

Molecular Disease Monitoring in Patients With Relapsed/refractory B-Cell Lymphoma Receiving Anti-CD19 CAR T-Cell Therapy

Article

作者: Kamdar, Manali ; Purev, Enkhtsetseg ; Jacob, Allison ; Colton, Meryl ; Jasem, Jagar ; Haverkos, Bradley ; Bair, Steven

BACKGROUNDChimeric antigen receptor (CAR) T-cell therapy has improved the historically poor outcomes for relapsed and refractory (R/R) large B-cell non-Hodgkin's lymphoma (LBCL). However, nearly 60% of patients will either fail to respond or relapse after CAR T-cell therapy. Currently, PET/CT scans are used to assess response. Cell-free circulating tumor DNA (ctDNA) is released by tumor cells into the peripheral blood and can be measured for minimal residual disease (MRD) assessment.METHODSIn this retrospective, IRB approved pilot study, archived lymphoma tissue and ctDNA from peripheral blood samples on day 0, 14, 28, 56, 90, 180, and 365 after CAR T-cell infusion from 10 patients with R/R NHL were collected for next-generation sequencing (NGS) of clonal variable-diversity-joining (VDJ) rearrangements (Adaptive biotechnologies [Seattle, WA]). Response was assessed by PET/CT on days 90 and 365 and graded according to the Lugano 2014 criteria. The primary endpoint was to determine the feasibility of detecting ctDNA to monitor disease response after anti-CD19 CAR T-cell therapy. The secondary endpoint was to compare the sensitivity/specificity of MRD assessment from ctDNA to PET/CT imaging.RESULTSNine out of 10 patients with a trackable sequence [median age 69 (range: 56-76); 55.6% male; median LDH 224], were included in this study. Each received tisagenlecleucel (tisa-cel) CAR T-cell therapy after median 2 prior treatments (range: 2-4). 7/9 patients had R/R diffuse large B-cell lymphoma (DLBCL), and 2/9 had transformed follicular lymphoma. At a median follow up of 12.7 months (range: 1.5-30 months), 4 patients were alive. By day 90, 3 patients (33.3%) achieved a radiographic complete response (CR) whilst 6 patients (66.6%) had progressive disease (PD). Detectable MRD on day 14 or day 28 had 83% sensitivity and 100% specificity for radiographic progression at any time before 1 year. For patients with PD, the median (interquartile range) MRD at day 0, 14, and 28 were 17.31 (1.01, 96.84), 9.12 (0.30, 18.8), and 23.77 (8.01, 137.53) copies per milliliter (mL), respectively. For patients with detectable MRD at day 28, mOS and mPFS were 6.7 and 1.3 months, respectively.CONCLUSIONMonitoring MRD was a sensitive and specific method to detect poor response to tisa-cel. Additional studies evaluating MRD more frequently and with different products are warranted.

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