Successful Continuation of Clozapine in Conjunction With Chimeric Antigen Receptor T-Cell (CAR-T) Immunotherapy: Case Report

Taking advantage of the cellular immune system is the mainstay of the adoptive cell therapy, to induce recognition and destruction of cancer cells. The impressive demonstration of this principle is chimeric antigen receptor-modified T (CAR-T)-cell therapy, which had a major impact on treating relapsed and refractory hematological malignancies. Despite the great results of the CAR-T-cell therapy, many tumors are still able to avoid immune detection and further elimination, as well as the possible associated adverse events. Herein, we highlighted the recent advances in CAR-T-cell therapy, discussing their applications beneficial functions and side effects in hematological malignancies, illustrating the underlying challenges and opportunities. Furthermore, we provide an overview to overcome different obstacles using potential manufacture and treatment strategies.

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Cancer stem cell-targeted chimeric antigen receptor (CAR)-T cell therapy: Challenges and prospects

Acta Pharmaceutica Sinica B ◽

10.1016/j.apsb.2020.12.015 ◽

2020 ◽

Author(s):

Javad Masoumi ◽

Abdollah Jafarzadeh ◽

Jalal Abdolalizadeh ◽

Haroon Khan ◽

Jeandet Philippe ◽

...

Keyword(s):

Stem Cell ◽

T Cell ◽

Cell Therapy ◽

Cancer Stem Cell ◽

Chimeric Antigen Receptor ◽

Antigen Receptor ◽

T Cell Therapy ◽

Car T Cell ◽

Car T Cell Therapy ◽

Car T

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Invasive Fungal Infections after Anti-CD19 Chimeric Antigen Receptor-Modified T-Cell Therapy: State of the Evidence and Future Directions

Journal of Fungi ◽

10.3390/jof7020156 ◽

2021 ◽

Vol 7 (2) ◽

pp. 156

Author(s):

Will Garner ◽

Palash Samanta ◽

Ghady Haidar

Keyword(s):

Risk Factors ◽

T Cell ◽

Cell Therapy ◽

Chimeric Antigen Receptor ◽

Fungal Infections ◽

Antigen Receptor ◽

Invasive Fungal Infections ◽

T Cell Therapy ◽

Car T Cell ◽

Car T

Studies describing invasive fungal infections (IFIs) after chimeric antigen receptor-modified T-cell (CAR-T-cell) therapy are limited. Although post-CAR-T-cell IFIs appear to be uncommon, they are associated with significant morbidity and mortality. Specific risk factors for IFIs in CAR-T-cell recipients have not been fully characterized and are often extrapolated from variables contributing to IFIs in patients with other hematologic malignancies or those undergoing hematopoietic cell transplant. Optimal prophylaxis strategies, including the use of yeast versus mold-active azoles, also remain ill-defined. Further research should investigate key risk factors for IFIs and establish an evidence-based approach to antifungal prophylaxis in these patients in order to improve clinical outcomes.

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Continuous Telemetry Monitoring in Chimeric Antigen Receptor (CAR) T-Cell Therapy Patients

Transplantation and Cellular Therapy ◽

10.1016/s2666-6367(21)00260-8 ◽

2021 ◽

Vol 27 (3) ◽

pp. S211-S212

Author(s):

Eddie Stephens ◽

Ansh Mehta ◽

Tanya Persoon ◽

Shannon Baker ◽

Remy David ◽

...

Keyword(s):

T Cell ◽

Cell Therapy ◽

Chimeric Antigen Receptor ◽

Antigen Receptor ◽

T Cell Therapy ◽

Car T Cell ◽

Car T Cell Therapy ◽

Car T

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HGG-05. REGRESSION OF RECURRENT GLIOBLASTOMA AFTER BORON NEUTRON CAPTURE THERAPY AND CHIMERIC ANTIGEN RECEPTOR T-CELL THERAPY IN A CHILD

Neuro-Oncology ◽

10.1093/neuonc/noaa222.296 ◽

2020 ◽

Vol 22 (Supplement_3) ◽

pp. iii345-iii345

Author(s):

Hsin-Hung Chen ◽

Yi-Wei Chen

Keyword(s):

T Cells ◽

T Cell ◽

Chimeric Antigen Receptor ◽

Boron Neutron Capture Therapy ◽

Neutron Capture ◽

Antigen Receptor ◽

Neutron Capture Therapy ◽

T Cell Therapy ◽

Boron Neutron Capture ◽

Car T

Abstract A 6 y/o girl with recurrent multifocal glioblastoma received 3 times of boron neutron capture therapy (BNCT) and chimeric antigen receptor (CAR)–engineered T cells targeting the tumor-associated antigen HER2. Multiple infusions of CAR T cells were administered over 30 days through intraventricular delivery routes. It was not associated with any toxic effects of grade 3 or higher. After BNCT and CAR T-cell treatment, regression of all existing intracranial lesions were observed, along with corresponding increases in levels of cytokines and immune cells in the cerebrospinal fluid, but new lesions recurred soon after the treatment. This clinical response continued for 14 months after the initiation of first recurrence.

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OP206 Expert Elicitation Of Probabilistic Distributions to Inform Survival Modelling of CD19 Chimeric Antigen Receptor T-Cell Therapies

International Journal of Technology Assessment in Health Care ◽

10.1017/s0266462320000951 ◽

2020 ◽

Vol 36 (S1) ◽

pp. 3-3

Author(s):

Niamh Carey ◽

Conor Hickey ◽

Laura Mc Cullagh ◽

Michael Barry

Keyword(s):

T Cell ◽

Chimeric Antigen Receptor ◽

Antigen Receptor ◽

Expert Elicitation ◽

Cell Transplant ◽

Major Advance ◽

Cell Therapies ◽

Risk Of Death ◽

Car T Cell ◽

Car T

IntroductionIn 2018, the National Centre for Pharmacoeconomics (NCPE) was commissioned to conduct a health technology assessment (HTA) of one of the first commercially available chimeric antigen receptor (CAR) T-cell therapies, tisagenlecleucel. CAR T-cells are a major advance in personalized cancer treatment, demonstrating promising outcomes in relapsed/refractory pediatric acute lymphoblastic leukemia (pALL). However, the results are based on short-term follow up, limiting their value in predicting long-term survival and leading to uncertainty about the most appropriate survival modeling method to employ. This study aimed to address these limitations by means of expert elicitation.MethodsAn expert elicitation method, the histogram technique, was employed. A predefined discrete numerical scale was presented in Microsoft Excel® and the expert was asked to place twenty crosses on a frequency chart. These crosses represented the expert's beliefs about the distribution of particular quantities. Each cross represented five percent of the probabilistic distribution. Individual distributions were then aggregated across experts using linear pooling.ResultsA total of seventeen experts were invited to take part; eight agreed to participate and five completed the exercise. Three experts did not consider tisagenlecleucel to be a “curative” therapy because patients had a higher risk of death, compared with the age- and sex-matched general population. The aggregated distributions indicated the five-year overall survival rate to be thirty-three percent (95% CI 8.65–56.88) in patients who do not receive a subsequent stem cell transplant and twenty percent (95% CI 2.38 -52.04) in those who do.ConclusionsThe results of this study will be used to calibrate CD19 CAR T-cell therapy survival estimates presented in HTA submissions to the NCPE to ensure more robust assessments. They will also be used to inform the construction of a de novo cost-utility model for examining the cost effectiveness of CD19 CAR T-cell therapies for relapsed/refractory pALL in the Irish healthcare setting.

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Safety profile of chimeric antigen receptor T-cell immunotherapies (CAR-T) in clinical practice

European Journal of Clinical Pharmacology ◽

10.1007/s00228-021-03106-z ◽

2021 ◽

Author(s):

Giulia Bonaldo ◽

Nicola Montanaro ◽

AlbertoVaccheri ◽

Domenico Motola

Keyword(s):

T Cell ◽

Chimeric Antigen Receptor ◽

Clinical Setting ◽

Safety Profile ◽

Antigen Receptor ◽

The United States ◽

Reporting Odds Ratio ◽

Cytokine Release ◽

Car T ◽

Age Range

Abstract Purpose Two chimeric antigen receptor T-cell (CAR-T) therapies have been approved in the United States (USA) in 2017 and Europe (EU) in 2018: axicabtagene ciloleucel and tisagenlecleucel. They contain the patient’s own T cells, which are extracted, genetically modified, and reinfused. Alongside the good efficacy results, the assessment of safety profile of these new therapies represents a great challenge. Our aim was to analyze the reports of the adverse drug reactions (ADR) after CAR-T administration as occurred in the real clinical setting. Methods We performed a retrospective observational study, collecting all the reports in EU (EudraVigilance, EV) and US (FAERS) databases of ADRs regarding axicabtagene ciloleucel and tisagenlecleucel. Both descriptive and statistical analyses were performed, the latter by using Reporting Odds Ratio (ROR). Results A total number of 1426 reports of suspected ADRs were retrieved in EudraVigilance and FAERS. Patients’ reported age reflected the age range for which the drugs are approved (18–64 years for axicabtagene ciloleucel and patients aged under 25 years for tisagenlecleucel). The most reported event was cytokine release syndrome (CRS), 185 events for tisagenlecleucel and 462 for axicabtagene ciloleucel in FAERS and 137 and 498, respectively, in EudraVigilance. A disproportionality was found comparing axicabtagene ciloleucel with tisagenlecleucel for the above-mentioned event: EV ROR 2.47, 95% CI 2.22–2.74, FAERS 1.89, 1.70–2.10. Conclusion CRS represents the major problem with the administration of CAR-T therapies. Our analysis has not revealed new ADRs; however, it supports the safety profile of CAR-T with new data from real clinical setting.

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