Graft-versus-host disease after anti-CD19 chimeric antigen receptor T-cell therapy following allogeneic hematopoietic cell transplantation: a transplant complications and paediatric diseases working parties joint EBMT study

Article

作者: Boreland, William ; Besley, Caroline ; Peric, Zinaida ; Graham, Charlotte ; Wynn, Robert F ; O’Reilly, Maeve ; Peczynski, Christophe ; Schubert, Maria-Luisa ; Schoemans, Helene ; van Gorkom, Gwendolyn ; Bader, Peter ; von Bonin, Malte ; Blaise, Didier ; Mielke, Stephan ; Kalwak, Krzysztof ; Güngör, Tayfun ; Ortí, Guillermo ; Sengeloev, Henrik ; Moiseev, Ivan ; Kwon, Mi ; Kröger, Nicolaus ; Potter, Victoria ; Balduzzi, Adriana ; Amrolia, Persis ; Ryhänen, Samppa ; Yakoub-Agha, Ibrahim ; Pichler, Herbert ; Penack, Olaf ; Torrent, Anna ; Calkoen, Friso ; O'Reilly, Maeve ; Wynn, Robert F. ; Koenecke, Christian ; Chalandon, Yves

In patients diagnosed with B-acute lymphoblastic leukemia (B-ALL) or B-non-Hodgkin's lymphoma (B-NHL) relapsing after allogeneic stem cell transplantation (allo-HCT), it is a standard practice to perform anti-CD19 chimeric antigen receptor (CAR) T-cell therapy. When collected from the patient after allo-HCT, the produced CAR-T cells are likely to be donor T-cell-derived, creating unknown safety risks due to their potential allo-reactivity. We therefore performed an EBMT registry-based study on the incidence of graft-versus-host disease (GvHD) in this setting. We included 257 allo-HCT patients (n = 172 ≥ 18 years) with B-ALL or B-NHL, treated with anti-CD19 CAR T-cells (tisagenlecleucel n = 184, brexucabtagene autoleucel n = 43 and axicabtagene ciloleucel n = 30), between 2018 and 2022. Three patients developed aGvHD, whereas 6 patients developed cGvHD after CAR T-cell. The 100-day cumulative incidence (CI) of new aGvHD was 1.6% and the 12-month CI of new cGvHD was 2.8%. The 1-year GvHD relapse-free survival and non-relapse mortality were 52.1% and 4.7%, respectively. Last, with a median follow up of 18.8 months, the 1-year overall survival was 76.8%. In summary, the GvHD rate in allo-HCT patients treated with CAR T-cell therapy is relatively low. Our data support the view that GvHD is not a major safety issue in this setting.

2025-01-01·Transplantation and Cellular Therapy

Prospective Validation of CAR-HEMATOTOX and a Simplified Version Predict Survival in Patients with Large B-Cell Lymphoma Treated with Anti-CD19 CAR T-Cells: Data from CART-SIE Study

Article

作者: Barone, Angelica ; Martino, Massimo ; Chiusolo, Patrizia ; Musso, Maurizio ; Bonifazi, Francesca ; Olivieri, Jacopo ; Cavallo, Federica ; Stella, Federico ; Brunello, Lucia ; Russo, Domenico ; Krampera, Mauro ; Farina, Lucia ; Cutini, Ilaria ; Sorà, Federica ; Santoro, Armando ; Pennisi, Martina ; Angelillo, Piera ; Grillo, Giovanni ; Novo, Mattia ; Corradini, Paolo ; Chiappella, Annalisa ; Barbui, Anna Maria ; Arcaini, Luca ; Tisi, Maria Chiara ; Casadei, Beatrice ; Ljevar, Silva ; Rocco, Alice Di ; Zinzani, Pierluigi ; Miceli, Rosalba ; Massaia, Massimo ; Bramanti, Stefania

BACKGROUNDAnti-CD19 CAR T-cells have revolutionized outcomes in relapsed/refractory large B-cell lymphomas. Long-term follow-up underscored the role of hematological toxicity in non-relapse mortality, largely driven by infections, leading to the development of the CAR-HEMATOTOX (HT) score for predicting neutropenia. The European scientific community (EHA/EBMT) later reached a consensus, defining a new entity: immune effector cell-associated hematotoxicity (ICAHT).AIMSTo validate the ability of the HT score to predict ICAHT and survival.METHODSThe CART-SIE is an ongoing multicenter prospective observational study collecting data on patients affected by B-cell lymphoma treated with commercial anti-CD19 CAR T-cells (ClinicalTrials.gov ID: NCT06339255).RESULTSSince 2019 to 2024, 1002 consecutive patients were enrolled. Out of 746 patients infused, the HT score at infusion was evaluable in 389. Median age was 59 years (48-66). Patients with high HT score had greater disease burden and a greater need for bridge therapy. Patients with a HT^HIGH score had a 4-fold higher risk of experiencing late ICAHT of grade≥3 (OR=3.99, _95%CI=1.16-13.77, p=0.03). Patients with a HT^HIGH score also showed lower overall response rates (ORR) and complete response rates (CRR) at 90 days (CRR at 90 days: 59% HT^LOW vs 38% HT^HIGH, OR=0.42, _95%CI=0.27-0.66, p=0.0002; ORR at 90 days: 67% HT^LOW vs 49% HT^HIGH, OR=0.47, _95%CI=0.29-0.74, p=0.001). Adjusted logistic models confirmed that the effect of HT score was independent from baseline characteristics. With a median follow-up of 18 months, patients with a HT^HIGH score have lower OS and PFS (1-year OS: 78% HT^LOW versus 62% HT^HIGH, p=0.0002; 1-year PFS: 49% versus 39%, p=0.003). Adjusted Cox models confirmed that HT was an independent prognostic factor for OS. A high HT-score was found to be associated with higher risk of secondary primary malignancy (HR=2.8, _95%CI=1.03-7.8, p=0.04). A simplified version of HT (simpleHT), based solely on the platelet count and C-reactive protein at infusion, was calculated for 560 patients and proved significant in predicting both OS and PFS (1-year was 72% simpleHT^LOW vs 37% simpleHT^HIGH, p<0.0001, 1-year PFS was 48% simpleHT^LOW vs 22% simpleHT^HIGH, p<0.0001).CONCLUSIONIn our prospective real-world study, we validated the ability of the HT score to predict ICAHT and survival. SimpleHT identified a population at very high risk with an impaired progression free and overall survival.

2024-12-01·Autoimmunity Reviews

Harnessing the potential of CAR-T cell in lupus treatment: From theory to practice

Review

作者: Schett, Georg ; Avcin, Tadej ; Hagen, Melanie ; Tarte, Karin ; Rimar, Doron ; Marjanovic, Zora ; Alsuliman, Tamim ; Farge, Dominique

Systemic Lupus Erythematosus (SLE) is a rare, heterogeneous, potentially life-threatening autoimmune disease. Presence of kidney or other major organ (brain, heart or lung) involvement are predictors of poor outcome and in a subset of patients resistant to 1st or 2nd line conventional treatment. The 10-year mortality remains around 10-15 %. Chimeric Antigen Receptors (CAR) are molecules that allow to redirect the engineered immune cells towards specific target antigens and to simultaneously boost their activation. Following breakthrough results observed in the treatment of hematological malignancies, conventional CAR T-cell therapy has recently been applied to refractory SLE patients. Compared to the use of monoclonal antibodies, anti-CD19 CAR T-cells allow to achieve deeper depletion of autoreactive B cells, notably at site of inflamed tissues and lymphoid organs (i.e. lymph node), to suppress interferon signature and to restore the immune tolerance with the reemergence of naïve B-cells with a new repertoire. All clinical data reported in SLE patients so far showed that autologous anti-CD19 CAR T-cell treatment allowed impressive short- and longer-term resolution of lupus nephritis and other severe disease-related manifestations, without major toxicities and only mild cytokine-release syndrome. These clinical effects persisted after B-cell reconstitution and were associated with normalization of double-stranded DNA antibodies and complement levels in drug-free patients until three years after the procedure. Overall, these pioneering experiences show unique clinical and immunological response to CAR T-cell therapy in SLE, and the need for extended follow-up to determine its long-term efficacy.

项与 Anti-CD19 CAR T-cells(Antion Biosciences) 相关的新闻（医药）

2024-05-22

·GlobeNewswire-Health Care

Antion Biosciences announces development of safety-enhanced and off-the-shelf CAR T-cells for autoimmune disease

Aiming for a best-in-class solution to treat and cure B-cell driven autoimmune diseasesGENEVA, May 22, 2024 (GLOBE NEWSWIRE) -- Antion Biosciences (Antion), a Geneva-based cell and gene therapy company developing “off-the-shelf” cell therapies, announces the development of next generation anti-CD19 chimeric antigen receptor (CAR) T-cells for B-cell driven autoimmune diseases. Autoimmunity affects up to 10% of the global population, and the overall burden of care is believed to well-exceed US $120 billion per annum. Recent findings indicate that targeted CAR T-cell therapy is very effective in severe cases of autoimmune disease. According to pioneer, Prof. Dr. Georg Schett, one of Time Magazines Most Influential People in Health, “Not only are the patients in drug-free remission, but I believe many are cured of their autoimmune disease.” The findings have sparked the interest of numerous groups, including the likes of Novartis to pursue the opportunity. Dr. Marco Alessandrini, PhD, CEO of Antion, believes this signals a paradigm shift in the way autoimmune disease will be treated in future, offering unique opportunities to create life-transforming therapies for millions. “Our approach is to anticipate the future need and develop a product that will stand the test of time.” Antion’s “miCAR19” is a multiplex engineered therapeutic, designed to address key constraints of existing products in development. First and foremost, it addresses the question of patient safety. Chemotherapeutic pre-conditioning is the status quo for all CAR T-cell products in oncology; but this is not desirable, and in most cases unacceptable, for treating patients with autoimmune disease. Antion’s safety-enhanced product is gene engineered to circumvent the need for pre-conditioning, while also mitigating further hyperinflammatory risks. Being an allogenic product, it not only enables off-the-shelf provision, but also facilitates scaled manufacturing to meet the global demand for this potentially curative therapy. “This is the start of a new chapter in Antion. Our technology platform has shown its worth in our hands and in the hands of our partners, so I’m convinced we will develop a robust product. Progressing it to clinic as rapidly as possible is our number one priority,” noted Dr. Alessandrini. About Antion BiosciencesAntion Biosciences SA is a Swiss-based biotechnology company developing cell and gene therapy products for the treatment of diseases with significant unmet medical needs. Antion’s proprietary technology platform allows for a modular and tunable approach to multiplex engineering of therapeutic cells. Through development of off-the-shelf and immune privileged products, our vision is to broaden access to these life-changing therapies for all patients. For more information, please visit https://www.antionbio.com. Antion's Cautionary Note on Forward-Looking StatementsPlease note: This announcement can contain forward-looking statements based on current expectations and projections about future events. Actual results may differ materially from those expressed or implied by these forward-looking statements due to various factors, including, but not limited to, market conditions, industry trends, and operational risks. Antion Biosciences Contactmedia@antionbio.comAntion Biosciences SAChemin des Aulx 12, CTN121228 Plan-les-OuatesGenevaSwitzerland

细胞疗法基因疗法免疫疗法

2024-05-22

·BioSpace

Antion Biosciences announces development of safety-enhanced and off-the-shelf CAR T-cells for autoimmune diseaseAiming for a best-in-class solution to treat and cure B-cell driven autoimmune diseases

GENEVA, May 22, 2024 (GLOBE NEWSWIRE) -- Antion Biosciences (Antion), a Geneva-based cell and gene therapy company developing “off-the-shelf” cell therapies, announces the development of next generation anti-CD19 chimeric antigen receptor (CAR) T-cells for B-cell driven autoimmune diseases. Autoimmunity affects up to 10% of the global population, and the overall burden of care is believed to well-exceed US $120 billion per annum. Recent findings indicate that targeted CAR T-cell therapy is very effective in severe cases of autoimmune disease. According to pioneer, Prof. Dr. Georg Schett, one of Time Magazines Most Influential People in Health, “Not only are the patients in drug-free remission, but I believe many are cured of their autoimmune disease.” The findings have sparked the interest of numerous groups, including the likes of Novartis to pursue the opportunity. Dr. Marco Alessandrini, PhD, CEO of Antion, believes this signals a paradigm shift in the way autoimmune disease will be treated in future, offering unique opportunities to create life-transforming therapies for millions. “Our approach is to anticipate the future need and develop a product that will stand the test of time.” Antion’s “miCAR19” is a multiplex engineered therapeutic, designed to address key constraints of existing products in development. First and foremost, it addresses the question of patient safety. Chemotherapeutic pre-conditioning is the status quo for all CAR T-cell products in oncology; but this is not desirable, and in most cases unacceptable, for treating patients with autoimmune disease. Antion’s safety-enhanced product is gene engineered to circumvent the need for pre-conditioning, while also mitigating further hyperinflammatory risks. Being an allogenic product, it not only enables off-the-shelf provision, but also facilitates scaled manufacturing to meet the global demand for this potentially curative therapy. “This is the start of a new chapter in Antion. Our technology platform has shown its worth in our hands and in the hands of our partners, so I’m convinced we will develop a robust product. Progressing it to clinic as rapidly as possible is our number one priority,” noted Dr. Alessandrini. About Antion Biosciences Antion Biosciences SA is a Swiss-based biotechnology company developing cell and gene therapy products for the treatment of diseases with significant unmet medical needs. Antion’s proprietary technology platform allows for a modular and tunable approach to multiplex engineering of therapeutic cells. Through development of off-the-shelf and immune privileged products, our vision is to broaden access to these life-changing therapies for all patients. For more information, please visit . Antion's Cautionary Note on Forward-Looking Statements Please note: This announcement can contain forward-looking statements based on current expectations and projections about future events. Actual results may differ materially from those expressed or implied by these forward-looking statements due to various factors, including, but not limited to, market conditions, industry trends, and operational risks. Antion Biosciences Contact media@antionbio.com Antion Biosciences SA Chemin des Aulx 12, CTN12 1228 Plan-les-Ouates Geneva Switzerland

细胞疗法免疫疗法基因疗法

100 项与 Anti-CD19 CAR T-cells(Antion Biosciences) 相关的药物交易

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