scholarly journals SARS‐CoV‐2 Vaccine Response in CAR T‐cell Therapy Recipients: A Systematic Review and Preliminary Observations

2021 ◽  
Author(s):  
Muhammad Abbas Abid ◽  
Muhammad Bilal Abid
Keyword(s):  
Systematic Review ◽  
T Cell ◽  
Cell Therapy ◽  
Vaccine Response ◽  
T Cell Therapy ◽  
Car T Cell ◽  
Car T Cell Therapy ◽  
Car T

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 Outcomes with "Off the Shelf" Allogeneic CD19 Chimeric Antigen Receptor T Cell Therapy for Hematological Malignancies: A Systematic Review and Meta-Analysis

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4831-4831
Author(s):  
Muhammad Umair Mushtaq ◽  
Moazzam Shahzad ◽  
Ali Hussain ◽  
Amna Y Shah ◽  
Raheel S Siddiqui ◽  
...  
Keyword(s):  
Systematic Review ◽  
Clinical Trials ◽  
T Cell ◽  
Cell Therapy ◽  
Research Funding ◽  
Meta Analysis ◽  
T Cell Therapy ◽  
Car T Cell ◽  
Car T Cell Therapy ◽  
Car T

Abstract Background: Chimeric antigen receptor T cell (CAR-T) therapy is an adoptive T cell immunotherapy that employs the genetically modified T cell to attack the cancer cell. It is widely studied across various hematological and solid organ malignancies. Several autologous CD19 CAR-T cell therapy constructs are now approved for various B cell lymphomas, including aggressive B cell lymphomas, indolent follicular lymphoma and mantle cell lymphoma, and acute lymphoblastic leukemia (ALL). Autologous CD19 CAR-T cell therapy has unprecedented success in relapsed and refractory disease. Long time to manufacture (2-5 weeks) and manufacture failure are challenges associated with risk of interim death and deterioration of CAR-T candidates with rapidly progressive disease. T cell fitness of the autologous product in heavily pretreated patients is also potentially compromised. To overcome these shortcomings, universal "off the shelf" allogeneic CAR-T cell therapy constructs are being developed and studied. Donor sources include healthy donors and cord or induced pluripotent stem cells (iPSCs). These CAR-T constructs have additional gene modifications to mitigate the risk of rejection and graft versus host disease (GVHD). We performed a systematic review and meta-analysis to assess the safety and efficacy of allogeneic CD19 CAR-T cell therapy. Methods: Four databases (Web of Science/MEDLINE/PubMed, Embase, and Cochrane Registry of Controlled Trials) were searched for this systematic review and meta-analysis following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines using MeSH terms and keywords for "Receptors, Chimeric antigen" OR "Artificial-T-cell receptor" OR "immunotherapy, adoptive" OR "CD-19". Our search produced 3506 articles and after removing duplicates, 2243 records were screened. After excluding reviews and irrelevant articles, we included 8 prospective trials of allogeneic CD-19 CAR-T cell therapy enrolling two or more than two patients from Jan 2013 to Nov 2020. We also searched ASH 2020 abstracts to include any additional trials. The methodological quality of the included studies was evaluated using NIH quality assessment tool. Inter-study variance was calculated using the Der Simonian-Laird Estimator. Proportions along with 95% confidence Interval (CI) were extracted to compute pooled analysis using the 'meta' package by Schwarzer et al. in the R programming language (version 4.16-2). Results: A total of 68 patients from 8 studies were evaluated. Median age was 22.5 (4.8-64) years. (Table 1) The median follow-up time was 10 (2-18) months with median number of prior therapies of 3.2 (2-11) as reported by 5 studies. Underlying diagnosis was acute lymphocytic lymphoma (n=49, 72%), chronic lymphocytic leukemia (n=6, 9%), and non-Hodgkin lymphoma (n=13, 19%). The pooled overall response rate (ORR) was 77% (95% CI 0.63-0.89, I 2 =22%, n=68) with a complete response (CR) of 75% (95% CI 0.57-0.90, I 2 =48%, n=65). The pooled incidence of cytokine release syndrome grade I/II and grade III/IV was 53% (95% CI 0.16-0.89, I 2 =89%, n=65) and 10% (95% CI 0.01-0.25, I 2 =50%, n=65) respectively. Neurotoxicity grade I/II was 12% (95%CI 0.01-0.30, I 2 =47%, p=0.09, n=47) and GVHD grade I/II was 8% (95%CI 0.01-0.19, I 2 =0%, p=0.57 n=53). None of the clinical trials reported the duration of response. Conclusion: "Off the shelf" universal CAR-T therapy is early in development. Our available data suggest that allogeneic CD19 CAR-T constructs offer high ORR and CR rates with acceptable safety profiles. GVHD was mainly low grade (grade I-II). Given these findings, allogeneic CAR-T cell therapy is an attractive option to improve timely access compared to available autologous therapy. Extensive preclinical research to develop novel constructs and several phase I/II clinical trials are ongoing to shape the future of "off the shelf" CAR-T cell therapy. Figure 1 Figure 1. Disclosures Hoffmann: Pharmcyclics: Consultancy, Honoraria; TG Therapeutics: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; celgene: Consultancy, Honoraria. Abhyankar: Incyte/Therakos: Consultancy, Research Funding, Speakers Bureau. McGuirk: Fresenius Biotech: Research Funding; Gamida Cell: Research Funding; Pluristem Therapeutics: Research Funding; EcoR1 Capital: Consultancy; Novartis: Research Funding; Astelllas Pharma: Research Funding; Kite/ Gilead: Consultancy, Honoraria, Other: travel accommodations, expense, Kite a Gilead company, Research Funding, Speakers Bureau; Juno Therapeutics: Consultancy, Honoraria, Research Funding; Magenta Therapeutics: Consultancy, Honoraria, Research Funding; Novartis: Research Funding; Bellicum Pharmaceuticals: Research Funding; Allovir: Consultancy, Honoraria, Research Funding.

scholarly journals Evolving Data on CAR T-Cell Therapy for Multiple Myeloma, Novel Targets, Conditioning Regimens and Novel Constructs: A Systematic Review

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5547-5547
Author(s):  
Yusra Shao ◽  
Daniel S Carlson ◽  
Faiz Anwer
Keyword(s):  
Systematic Review ◽  
T Cells ◽  
T Cell ◽  
Cell Therapy ◽  
Viral Vector ◽  
T Cell Therapy ◽  
Car T Cells ◽  
Car T Cell ◽  
Car T Cell Therapy ◽  
Car T

Introduction: Multiple myeloma (MM) remains an incurable malignancy originating from plasma cell. Chimeric antigen receptor T (CAR T) cells have been used for treating various malignancies and have proven very efficacious especially for some hematologic malignancies. Pre-clinical and phase 1 studies of CAR T-cells designed against various molecular targets in MM patients have demonstrated encouraging anti-tumor activity. With the emerging data and success of antibody based immunotherapy, questions about the clinical efficacy and safety of CAR T-cells continue to emerge. This study aims to provide a systematic review of CAR T-cell therapy in MM through systematic review offering a reference for future research. Methods: On 03/28/19, we performed a search for published studies on CAR T cell therapy in MM using the following databases: Embase, Web of Science, Biosis and Scopus. Following PRISMA guidelines, search results were screened by two independent reviewers. Clinical studies with safety and efficacy data were included in the analysis. In vitro and animal studies and abstracts with duplicate data were excluded. Results: Our literature search produced 1604 results and 21 studies were included in the final review. Of these, 7 were complete manuscripts. Publications were from 2016-2019. 1 was a clinical pilot study, 20 phase 1 trials and 1 study extending to phase 2 with unpublished data. Reported CAR-T cell targets were BCMA (trials [t]=14), CD138 (t=1), CD19 (t=1), Kappa light chain (t=1), multi ligand (t=1), NKG2D (t=1) and 2 studies combining anti BCMA and CD19 CAR T cell infusion. Viral vectors were gamma retrovirus (t=4), lentivirus (t=10), standard retrovirus (t=2), 1 trial without a viral vector and 4 with unknown viral vector. Source of single chain fragment variants were human (t=4), murine (t=3), alpaca (t=1) and 13 unknown. Number of treated MM patients evaluable for efficacy were 4-57. Median prior lines of therapy were 3-12.5 with 3 studies not reporting prior lines of therapy. Pre conditioning treatments were cyclophosphamide (t=4), cyclophosphamide and fludarabine (t=12), high dose melphalan and autologous stem cell transplantation (t=1), 1 trial without preconditioning and 3 with unknown pre conditioning regimen. Dose of CAR-T cell administered ranged from 2.1x10^6-3x10^9. Median follow up time was 2-35 weeks. Overall response rate was 0%-100%. Individual response rate was as follows: strict complete response (CR) 0%-21%, CR 0%-68%, near CR 0%-11%, partial response 0%-75%, minimal response 0%-20%, stable disease 0%-100%, progressive disease 0%-100%. Only two studies reported minimal residual disease negative response of 14%-63%. 11 studies reported median progression free survival (PFS) of 4.15 weeks-15 months. 10 studies reported number of patients with grade 3 or higher complications with a rate of complication of 0-96%. Conclusion: Results of trials using CAR-T cell therapy in MM are promising for heavily treated relapsed MM patients. BCMA has emerged as an appropriate target for CAR T based immunotherapy. Possibility of a longer lasting PFS makes this modality of treatment very desirable. Variability in safety and efficacy data may be related to patient related factors, disease severity, prior lines of therapy and may uniquely be linked with CAR-T cell construct. Larger prospective clinical studies and randomized control trials are needed to further study the role and safety issue with CAR T cell therapy in relapsed and refractory MM. Disclosures Anwer: In-Cyte: Speakers Bureau; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees.

Disparities in the use of checkpoint inhibitors and CAR T-cell therapy: A systematic review.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e18541-e18541
Author(s):  
Devika R. Jutagir ◽  
Adriana Espinosa ◽  
Melissa Lopez ◽  
Burha Rasool ◽  
Taisha Gomez ◽  
...  
Keyword(s):  
Systematic Review ◽  
T Cell ◽  
Cell Therapy ◽  
Checkpoint Inhibitors ◽  
The United States ◽  
Treatment Facility ◽  
T Cell Therapy ◽  
Car T Cell ◽  
Car T Cell Therapy ◽  
Car T

e18541 Background: With increasing numbers of newly approved cancer immunotherapy regimens, research is needed to understand whether these costly treatments are equally used by all patients who could benefit from them. The aim of this systematic review was to identify variables linked to whether patients diagnosed with cancer were treated with checkpoint inhibitors and chimeric antigen receptor (CAR) T-cell therapy. Methods: Using the PICO (Patient, Intervention, Comparison, Outcome) framework, we conducted a systematic review searching Medline (New PubMed), Embase.com, and the Cochrane Library (Wiley) for papers published in English between January 1, 1997 and July 27, 2020. Inclusion criteria were: 1) primary, peer-reviewed research article; and 2) article reported variables associated with whether patients were treated with checkpoint inhibitors or CAR T-cell therapy. Seven coders independently reviewed titles, abstracts, full texts, and extracted data. The systematic review adhered to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Results: In total, 5958 titles and abstracts and 134 full texts were screened. Sixteen studies were included in final analyses. All were conducted in the United States using data from national databases (N = 15) or electronic medical records (N = 1). Eleven were cross-sectional, and 5 were cohort studies. Studies looked at melanoma (N = 10), non-small cell lung cancer (N = 3), renal cell carcinoma (N = 2), colorectal cancer (N = 1), prostate cancer (N = 1), and hepatobiliary cancer (N = 1). Studies looked at nivolumab (N = 1), pembrolizumab (N = 1), ipilimumab (N = 1), and sipuleucel-T, (N = 1), and 12 studies did not specify medication names. Treatment facility characteristics (N = 9), geographic location within the United States (N = 1), locale classification (N = 2), distance to treatment facility (N = 2), insurance type (N = 9), age (N = 7), race (N = 5), sex (N = 1), income (N = 4), neighborhood educational attainment (N = 2), comorbidities (N = 6), disease stage (N = 1), metastases (N = 3), clinical trial participation (N = 1), recency of diagnosis (N = 2), other treatments received (N = 3), and lesion characteristics (N = 1) were reported to be associated with whether patients were treated with checkpoint inhibitors or CAR T-cell therapy. Other studies found that insurance type (N = 1), race (N = 3), sex (N = 1), other treatments received (N = 1), and lesion characteristics (N = 1) were not associated with receiving checkpoint inhibitors or CAR T-cell therapy. Conclusions: Findings provide evidence of disparate access to checkpoint inhibitors and CAR T-cell therapy. More studies are necessary to thoroughly understand how the factors highlighted in our findings intersect to create and maintain disparities in cancer treatment. This level of information is necessary to create interventions that promote equitable access to novel cancer immunotherapies.

Effect of transplant status in CD19-targeted CAR T-cell therapy: a systematic review and meta-analysis

2018 ◽  
Vol 35 (11) ◽  
Author(s):  
Kathleen Nagle ◽  
Barbara Tafuto ◽  
Lisa Palladino Kim ◽  
J. Scott Parrott
Keyword(s):  
Systematic Review ◽  
T Cell ◽  
Cell Therapy ◽  
Meta Analysis ◽  
T Cell Therapy ◽  
Car T Cell ◽  
Car T Cell Therapy ◽  
Car T

Anti-CD 19 and Anti- CD 20 Chimeric Antigen Receptor-Modified T Cells for B-Cell Malignancies: A Systematic Review and Meta-Analysis

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5163-5163 ◽  
Author(s):  
Irbaz Bin Riaz ◽  
Muhammad Husnain ◽  
Muhammad Umar Kamal ◽  
Ali McBride ◽  
Anh Hua ◽  
...  
Keyword(s):  
Systematic Review ◽  
T Cell ◽  
Cell Therapy ◽  
B Cell ◽  
Hematological Malignancies ◽  
Meta Analysis ◽  
T Cell Therapy ◽  
Car T Cell ◽  
Car T Cell Therapy ◽  
Car T

Abstract Background: Chimeric antigen receptor (CAR) modified T cells targeting CD19 and CD20 have shown activity in Phase I, II trials of patients with hematological malignancies. CD19 and CD20 targeted CAR constructs from several different institutions have demonstrated consistently high anti-tumor efficacy in children and adults with relapsed B-cell acute lymphoblastic leukemia (B-ALL), chronic lymphocytic leukemia (CLL) and B-cell non-Hodgkin lymphoma (B-NHL). We conducted a systematic review and meta-analysis of all published clinical trials studying the role of efficacy as well as safety of CD-19 and CD-20 CAR-T therapy for B-cell hematologic malignancies. Methods: Literature search was performed using MEDLINE (Ovid SP and PubMed), EMBASE, The Cochrane Library, Scopus and Web of Science. We conducted meta-analysis using random effects model using Comprehensive Metaanalysis 3.0. Heterogeneity was assessed using Q-statistic and it was quantified using I2statistic. Results: After a comprehensive literature search 4476 studies were identified and finally 15 eligible studies involving 121 patients were included in the final systematic review. The infused CAR T-cell dose was in the range of 0.76 x 106 to 3 x 107 cells/kg in seven trials and in the range of 0.8 x 107 cells to 3.3 x 109 cells/m2in 6 trials. Among 106 patients, the overall response to treatment after CAR T-cell infusion were 33% complete remission (CR), 30 % partial remission (PR), 21% stable disease (SD), and 8% progressive disease (PD). Three studies described response to immunotherapy as minimal residual disease negative (MRD-) and as no evidence of disease (NED) and after including it, the overall CR was 38%. Major adverse events included fever (38%), hypotension (23%), chills (29%), rigor (28%), fatigue 17% and dyspnea 10%. One patient died from cytokine release syndrome, which is potentially serious complication. Neurological symptoms require prompt recognition and management. Conclusion: CAR T cell therapy is a promising treatment for refractory and relapsed hematological malignancies. The durable responses of CAR T cell therapy help integrate it in standard treatment protocols. Patients who are refractory to standard salvage chemotherapy or relapse after allo - HSCT have overall poor prognosis and can potentially achieve remission again with CAR T cell therapy. Disclosures McBride: Sanofi: Research Funding. Anwer:Seattle Genetics: Other: Advisory Board Participant; Incyte: Speakers Bureau.

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