Factors associated with duration of response after CD19-specific CAR-T cell therapy for refractory/relapsed B-cell non-Hodgkin lymphoma.

2018 ◽  
Vol 36 (15_suppl) ◽  
pp. 7567-7567 ◽  
Author(s):  
Jordan Gauthier ◽  
Alexandre V. Hirayama ◽  
Kevin Anthony Hay ◽  
Daniel Li ◽  
Alyssa Sheih ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Therapy ◽  
B Cell ◽  
Hodgkin Lymphoma ◽  
T Cell Therapy ◽  
Factors Associated ◽  
Non Hodgkin Lymphoma ◽  
Car T Cell Therapy ◽  
Car T ◽  
Duration Of Response

scholarly journals A Phase 1 Dose Escalation Trial of Third Generation Chimeric Antigen Receptor (CAR) T-Cell Therapy for Relapsed and Refractory B-Cell Non Hodgkin Lymphoma

2021 ◽  
Author(s):  
◽  
Philip George
Keyword(s):  
New Zealand ◽  
T Cell ◽  
Cell Therapy ◽  
B Cell ◽  
Hodgkin Lymphoma ◽  
T Cell Therapy ◽  
Car T Cell ◽  
Non Hodgkin Lymphoma ◽  
Car T Cell Therapy ◽  
Car T

<p>Anti-CD19 Chimeric Antigen Receptor (CAR) T-cell therapy is shifting the treatment paradigm internationally for selected patients with relapsed and refractory B-cell Non- Hodgkin Lymphoma. Despite high response rates with durable responses achieved in a significant proportion of patients, over 50% of patients will have progressed at one year following treatment with the currently licensed anti-CD19 CAR T-cell therapies. This modality of therapy is also associated with acute and potentially life-threatening toxicities, requiring strict risk mitigation strategies.  In this thesis, the design, preparation and implementation of a new third generation anti-CD19 CAR T-cell Phase 1 trial entitled ENABLE, for patients with relapsed and refractory B-cell Non-Hodgkin Lymphoma, is described in detail. Following a literature review of CAR T-cell therapy in patients with B-cell Non-Hodgkin Lymphoma, the rationale for the ENABLE trial design is discussed, along with regulatory and clinical requirements for setting up CAR T-cell therapy in New Zealand. The importance of international collaboration to inform aspects of study design, CAR T-cell product manufacturing and developing CAR T-cell toxicity management protocols, has been demonstrated.  The early clinical experience on the ENABLE trial is presented along with provisional safety, pharmacokinetic and efficacy data from the first participant treated. This is the first time that CAR T-cell therapy has been administered in New Zealand, demonstrating CAR T-cell expansion in vivo; but also highlighting the complexities of the CAR T-cell product manufacturing process and the importance of evaluating feasibility of CAR T-cell manufacturing, as a key secondary endpoint of the study. Further clinical experience on the ENABLE trial is crucial to develop the potential for CAR T-Cell therapy to be a safe, feasible and effective option for selected New Zealand patients in the future.</p>

scholarly journals Chimeric antigen receptor T‑cell therapy for B-cell non-Hodgkin lymphoma: opportunities and challenges

2021 ◽  
Vol 67 (3) ◽  
pp. 350-360
Author(s):  
Irina Gribkova ◽  
Aleksandr Zavyalov
Keyword(s):  
T Cell ◽  
Cell Therapy ◽  
B Cell ◽  
Hodgkin Lymphoma ◽  
Chimeric Antigen Receptor ◽  
T Cell Therapy ◽  
Car T Cell ◽  
Non Hodgkin Lymphoma ◽  
Car T Cell Therapy ◽  
Car T

B-cell non-Hodgkin lymphoma (NHL) is the most common hematologic malignant neoplasm. Despite the improvement of immunochemotherapy, a significant number of patients have a refractory form of the disease. CAR T-cell therapy (therapy with T-lymphocytes with a chimeric antigen receptor (CAR)) is considered the most promising and effective therapy for overcoming chemorefractory B-cell NHL. Based on promising results from key studies, the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) have approved anti-CD19 CAR T-cell therapy for relapsing / refractory diffuse B-cell lymphoma. However, several controversial issues remain, including the optimal management of toxicity, overcoming relapses after CAR T-cell therapy, and improving the production platform of CAR T-cells. This review describes the results of recent clinical research and development, as well as the prospects for the development of CAR T-cell therapy for B-cell NHL.

scholarly journals A Phase 1 Dose Escalation Trial of Third Generation Chimeric Antigen Receptor (CAR) T-Cell Therapy for Relapsed and Refractory B-Cell Non Hodgkin Lymphoma

2021 ◽  
Author(s):  
◽  
Philip George
Keyword(s):  
New Zealand ◽  
T Cell ◽  
Cell Therapy ◽  
B Cell ◽  
Hodgkin Lymphoma ◽  
T Cell Therapy ◽  
Car T Cell ◽  
Non Hodgkin Lymphoma ◽  
Car T Cell Therapy ◽  
Car T

<p>Anti-CD19 Chimeric Antigen Receptor (CAR) T-cell therapy is shifting the treatment paradigm internationally for selected patients with relapsed and refractory B-cell Non- Hodgkin Lymphoma. Despite high response rates with durable responses achieved in a significant proportion of patients, over 50% of patients will have progressed at one year following treatment with the currently licensed anti-CD19 CAR T-cell therapies. This modality of therapy is also associated with acute and potentially life-threatening toxicities, requiring strict risk mitigation strategies.  In this thesis, the design, preparation and implementation of a new third generation anti-CD19 CAR T-cell Phase 1 trial entitled ENABLE, for patients with relapsed and refractory B-cell Non-Hodgkin Lymphoma, is described in detail. Following a literature review of CAR T-cell therapy in patients with B-cell Non-Hodgkin Lymphoma, the rationale for the ENABLE trial design is discussed, along with regulatory and clinical requirements for setting up CAR T-cell therapy in New Zealand. The importance of international collaboration to inform aspects of study design, CAR T-cell product manufacturing and developing CAR T-cell toxicity management protocols, has been demonstrated.  The early clinical experience on the ENABLE trial is presented along with provisional safety, pharmacokinetic and efficacy data from the first participant treated. This is the first time that CAR T-cell therapy has been administered in New Zealand, demonstrating CAR T-cell expansion in vivo; but also highlighting the complexities of the CAR T-cell product manufacturing process and the importance of evaluating feasibility of CAR T-cell manufacturing, as a key secondary endpoint of the study. Further clinical experience on the ENABLE trial is crucial to develop the potential for CAR T-Cell therapy to be a safe, feasible and effective option for selected New Zealand patients in the future.</p>

scholarly journals Factors associated with durable EFS in adult B-cell ALL patients achieving MRD-negative CR after CD19 CAR T-cell therapy

Blood ◽  
2019 ◽  
Vol 133 (15) ◽  
pp. 1652-1663 ◽  
Author(s):  
Kevin A. Hay ◽  
Jordan Gauthier ◽  
Alexandre V. Hirayama ◽  
Jenna M. Voutsinas ◽  
Qian Wu ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
T Cell ◽  
Cell Therapy ◽  
B Cell ◽  
Lymphoblastic Leukemia ◽  
T Cell Therapy ◽  
Factors Associated ◽  
Car T Cell ◽  
Car T Cell Therapy ◽  
Car T

Abstract Autologous T cells engineered to express a CD19-specific chimeric antigen receptor (CAR) have produced impressive minimal residual disease–negative (MRD-negative) complete remission (CR) rates in patients with relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL). However, the factors associated with durable remissions after CAR T-cell therapy have not been fully elucidated. We studied patients with relapsed/refractory B-ALL enrolled in a phase 1/2 clinical trial evaluating lymphodepletion chemotherapy followed by CD19 CAR T-cell therapy at our institution. Forty-five (85%) of 53 patients who received CD19 CAR T-cell therapy and were evaluable for response achieved MRD-negative CR by high-resolution flow cytometry. With a median follow-up of 30.9 months, event-free survival (EFS) and overall survival (OS) were significantly better in the patients who achieved MRD-negative CR compared with those who did not (median EFS, 7.6 vs 0.8 months; P &lt; .0001; median OS, 20.0 vs 5.0 months; P = .014). In patients who achieved MRD-negative CR by flow cytometry, absence of the index malignant clone by IGH deep sequencing was associated with better EFS (P = .034). Stepwise multivariable modeling in patients achieving MRD-negative CR showed that lower prelymphodepletion lactate dehydrogenase concentration (hazard ratio [HR], 1.38 per 100 U/L increment increase), higher prelymphodepletion platelet count (HR, 0.74 per 50 000/μL increment increase), incorporation of fludarabine into the lymphodepletion regimen (HR, 0.25), and allogeneic hematopoietic cell transplantation (HCT) after CAR T-cell therapy (HR, 0.39) were associated with better EFS. These data allow identification of patients at higher risk of relapse after CAR T-cell immunotherapy who might benefit from consolidation strategies such as allogeneic HCT. This trial was registered at www.clinicaltrials.gov as #NCT01865617.

scholarly journals Infectious Complications of CAR T-Cell Therapy in Non-Hodgkin Lymphoma

2020 ◽  
Vol 26 (3) ◽  
pp. S275
Author(s):  
Justin Hayne ◽  
Jilan Kubusek ◽  
Pritish K. Tosh ◽  
Nora N. Bennani ◽  
Yi Lin ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Therapy ◽  
Hodgkin Lymphoma ◽  
Infectious Complications ◽  
T Cell Therapy ◽  
Car T Cell ◽  
Non Hodgkin Lymphoma ◽  
Car T Cell Therapy ◽  
Car T
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