scholarly journals Anti-CD30 CAR-T Cell Therapy in Relapsed and Refractory Hodgkin Lymphoma

2020 ◽  
Vol 38 (32) ◽  
pp. 3794-3804 ◽  
Author(s):  
Carlos A. Ramos ◽  
Natalie S. Grover ◽  
Anne W. Beaven ◽  
Premal D. Lulla ◽  
Meng-Fen Wu ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Therapy ◽  
B Cell ◽  
Hodgkin Lymphoma ◽  
High Rate ◽  
B Cell Malignancies ◽  
T Cell Therapy ◽  
Car T Cell ◽  
Car T Cell Therapy ◽  
Car T

PURPOSE Chimeric antigen receptor (CAR) T-cell therapy of B-cell malignancies has proved to be effective. We show how the same approach of CAR T cells specific for CD30 (CD30.CAR-Ts) can be used to treat Hodgkin lymphoma (HL). METHODS We conducted 2 parallel phase I/II studies (ClinicalTrials.gov identifiers: NCT02690545 and NCT02917083 ) at 2 independent centers involving patients with relapsed or refractory HL and administered CD30.CAR-Ts after lymphodepletion with either bendamustine alone, bendamustine and fludarabine, or cyclophosphamide and fludarabine. The primary end point was safety. RESULTS Forty-one patients received CD30.CAR-Ts. Treated patients had a median of 7 prior lines of therapy (range, 2-23), including brentuximab vedotin, checkpoint inhibitors, and autologous or allogeneic stem cell transplantation. The most common toxicities were grade 3 or higher hematologic adverse events. Cytokine release syndrome was observed in 10 patients, all of which were grade 1. No neurologic toxicity was observed. The overall response rate in the 32 patients with active disease who received fludarabine-based lymphodepletion was 72%, including 19 patients (59%) with complete response. With a median follow-up of 533 days, the 1-year progression-free survival and overall survival for all evaluable patients were 36% (95% CI, 21% to 51%) and 94% (95% CI, 79% to 99%), respectively. CAR-T cell expansion in vivo was cell dose dependent. CONCLUSION Heavily pretreated patients with relapsed or refractory HL who received fludarabine-based lymphodepletion followed by CD30.CAR-Ts had a high rate of durable responses with an excellent safety profile, highlighting the feasibility of extending CAR-T cell therapies beyond canonical B-cell malignancies.

scholarly journals Efficacy and safety of CD22 chimeric antigen receptor (CAR) T cell therapy in patients with B cell malignancies: a protocol for a systematic review and meta-analysis

2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Komal Adeel ◽  
Nathan J. Fergusson ◽  
Risa Shorr ◽  
Harold Atkins ◽  
Kevin A. Hay
Keyword(s):  
Systematic Review ◽  
Clinical Trials ◽  
T Cell ◽  
Cell Therapy ◽  
B Cell ◽  
B Cell Malignancies ◽  
T Cell Therapy ◽  
Car T Cell ◽  
Car T Cell Therapy ◽  
Car T

Abstract Background Chimeric antigen receptor (CAR) T cell therapy has had great success in treating patients with relapsed or refractory B cell malignancies, with CD19-targeting therapies now approved in many countries. However, a subset of patients fails to respond or relapse after CD19 CAR T cell therapy, in part due to antigen loss, which has prompted the search for alternative antigen targets. CD22 is another antigen found on the surface of B cells. CARs targeting CD22 alone or in combination with other antigens have been investigated in several pre-clinical and clinical trials. Given the heterogeneity and small size of CAR T cell therapy clinical trials, systematic reviews are needed to evaluate their efficacy and safety. Here, we propose a systematic review of CAR T cell therapies targeting CD22, alone or in combination with other antigen targets, in B cell malignancies. Methods We will perform a systematic search of EMBASE, MEDLINE, Web of Science, Cochrane Register of Controlled Trials, clinicaltrials.gov, and the International Clinical Trials Registry Platform. Ongoing and completed clinical trials will be identified and cataloged. Interventional studies investigating CD22 CAR T cells, including various multi-antigen targeting approaches, in patients with relapsed or refractory B cell malignancies will be eligible for inclusion. Only full-text articles, conference abstracts, letters, and case reports will be considered. Our primary outcome will be a complete response, defined as absence of detectable cancer. Secondary outcomes will include adverse events, overall response, minimal residual disease, and relapse, among others. Quality assessment will be performed using a modified Institute of Health Economics tool designed for interventional single-arm studies. We will report a narrative synthesis of clinical studies, presented in tabular format. If appropriate, a meta-analysis will be performed using a random effects model to synthesize results. Discussion The results of the proposed review will help inform clinicians, patients, and other stakeholders of the risks and benefits of CD22 CAR T cell therapies. It will identify gaps or inconsistencies in outcome reporting and help to guide future clinical trials investigating CAR T cells. Systematic review registration PROSPERO registration number: CRD42020193027

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>

Updates on CAR T-cell therapy in B-cell malignancies

2019 ◽  
Vol 290 (1) ◽  
pp. 39-59 ◽  
Author(s):  
Elad Jacoby ◽  
Shilpa A. Shahani ◽  
Nirali N. Shah
Keyword(s):  
T Cell ◽  
Cell Therapy ◽  
B Cell ◽  
B Cell Malignancies ◽  
T Cell Therapy ◽  
Car T Cell ◽  
Car T Cell Therapy ◽  
Car T

scholarly journals Resistance Mechanisms to CAR T-Cell Therapy and Overcoming Strategy in B-Cell Hematologic Malignancies

2019 ◽  
Vol 20 (20) ◽  
pp. 5010 ◽  
Author(s):  
Moo-Kon Song ◽  
Byeong-Bae Park ◽  
Ji-Eun Uhm
Keyword(s):  
T Cell ◽  
Cell Therapy ◽  
B Cell ◽  
Hematologic Malignancies ◽  
Resistance Mechanisms ◽  
B Cell Malignancies ◽  
T Cell Therapy ◽  
Car T Cell ◽  
Car T Cell Therapy ◽  
Car T

Chimeric antigen receptor (CAR) T-cell therapy has shown promising clinical impact against hematologic malignancies. CD19 is a marker on the surface of normal B cells as well as most B-cell malignancies, and thus has a role as an effective target for CAR T-cell therapy. In numerous clinical data, successes with cell therapy have provided anticancer therapy as a potential therapeutic option for patients who are resistant to standard chemotherapies. However, recent growing evidence showed the limitations of the treatment such as antigen-positive relapse due to poor CAR T-cell persistence and antigen-negative relapses associated with CAR-driven mutations, alternative splicing, epitope masking, low antigen density, and lineage switching. The understanding of the resistance mechanisms to the cell therapy has developed novel potential treatment strategies, including dual-targeting therapy (dual and tandem CAR), and armored and universal CAR T-cell therapies. In this review, we provide an overview of resistance mechanisms to CD19 CAR T-cell therapy in B-cell malignancies and also review therapeutic strategies to overcome these resistances.

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 Anti-CD22 CAR-T Cell Therapy as a Salvage Treatment in B Cell Malignancies Refractory or Relapsed After Anti-CD19 CAR-T therapy

2021 ◽  
Vol Volume 14 ◽  
pp. 4023-4037
Author(s):  
Haibo Zhu ◽  
Haobin Deng ◽  
Juan Mu ◽  
Cuicui Lyu ◽  
Yanyu Jiang ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Therapy ◽  
B Cell ◽  
Salvage Treatment ◽  
B Cell Malignancies ◽  
T Cell Therapy ◽  
Car T Cell ◽  
Car T Cell Therapy ◽  
Car T
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