scholarly journals Cardiotoxicity Associated with Anti-CD19 Chimeric Antigen Receptor T-Cell (CAR-T) Therapy: Recognition, Risk Factors, and Management

Diseases ◽  
2021 ◽  
Vol 9 (1) ◽  
pp. 20
Author(s):  
Ethan A. Burns ◽  
Cesar Gentille ◽  
Barry Trachtenberg ◽  
Sai Ravi Pingali ◽  
Kartik Anand
Keyword(s):  
Risk Factors ◽  
Chimeric Antigen Receptor ◽  
Antigen Receptor ◽  
Length Of Hospital Stay ◽  
Clinical Trial Data ◽  
Cardiac Events ◽  
Prolonged Length ◽  
Non Hodgkin Lymphoma ◽  
Car T ◽  
Potential Risk Factors

Chimeric antigen receptor T-cells (CAR-T) are improving outcomes in pediatric and adult patients with relapsed or refractory B-cell acute lymphoblastic leukemias and subtypes of non-Hodgkin Lymphoma. As this treatment is being increasingly utilized, a better understanding of the unique toxicities associated with this therapy is warranted. While there is growing knowledge on the diagnosis and treatment of cytokine release syndrome (CRS), relatively little is known about the associated cardiac events that occur with CRS that may result in prolonged length of hospital stay, admission to the intensive care unit for pressor support, or cardiac death. This review focuses on the various manifestations of cardiotoxicity, potential risk factors, real world and clinical trial data on prevalence of reported cardiotoxicity events, and treatment recommendations.

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

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.

scholarly journals Cardiac Events Associated With Chimeric Antigen Receptor T-Cells (CAR-T)

2020 ◽  
Vol 75 (19) ◽  
pp. 2521-2523
Author(s):  
Joe-Elie Salem ◽  
Stéphane Ederhy ◽  
Benedicte Lebrun-Vignes ◽  
Javid J. Moslehi
Keyword(s):  
T Cells ◽  
Chimeric Antigen Receptor ◽  
Antigen Receptor ◽  
Cardiac Events ◽  
Car T

Predictors of manufacturing (MFG) success for chimeric antigen receptor (CAR) T cells in Non-Hodgkin Lymphoma (NHL)

Cytotherapy ◽  
2017 ◽  
Vol 19 (5) ◽  
pp. S118-S119 ◽  
Author(s):  
M.M. Davis ◽  
A. Fesnak ◽  
R.M. Leskowitz ◽  
J.S. McKee ◽  
Y. Ohayon ◽  
...  
Keyword(s):  
T Cells ◽  
Hodgkin Lymphoma ◽  
Chimeric Antigen Receptor ◽  
Antigen Receptor ◽  
Car T Cells ◽  
Non Hodgkin Lymphoma ◽  
Car T

scholarly journals Clinical Characterization and Risk Factors Associated with Cytokine Release Syndrome Induced By COVID-19 and Chimeric Antigen Receptor T-Cell Therapy

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 35-36
Author(s):  
Ruimin Hong ◽  
Houli Zhao ◽  
Yiyun Wang ◽  
Yu Chen ◽  
Hongliu Cai ◽  
...  
Keyword(s):  
Risk Factors ◽  
T Cell ◽  
Cell Therapy ◽  
Chimeric Antigen Receptor ◽  
Antigen Receptor ◽  
Tumor Burden ◽  
Cytokine Release ◽  
Cytokine Release Syndrome ◽  
T Cell Therapy ◽  
Car T

Background: An excessive immune response during coronavirus disease (COVID-19) can induce cytokine release syndrome (CRS), which is associated with life-threatening complications and disease progression. Methods: This study was aimed to investigate the differences and similarities between CRS induced by COVID-19 and CAR-T therapy, then provide valuable experiences for early identification and controlling CRS progression in COVID-19. We retrospectively evaluated the clinical characteristics of severe CRS (sCRS, grade 3-4) induced by COVID-19 (40 patients) or chimeric antigen receptor T-cell (CAR-T) therapy as a comparator (41 patients). Results: Grade 4 CRS was significantly more common in the COVID-19 group (15/40 [35.7%] vs. 5/41 [12.2%], P=0.008). CAR-T group had more more dramatic increase in cytokine than COVID-19 group (Figure1), including IL-2 (7.3pg/mL [IQR: 2.0-12.7] vs.1.7 [0.7-2.7], P<0.001), IL-6 (7120.6 pg/mL [1066.8-15 136.4] vs. 110.3 [41.7-728.1], P<0.001), IL-10 (174.5pg/mL [61.7, 434.6] vs. 10.1 [6.3-20.6], P<0.001) and IFN-γ (1308.5pg/mL [296.6, 3108.2] vs .35.0 [16.9-60.8], P<0.001). Interestingly, COVID-19 group had significantly higher levels for TNF-α (31.1 pg/ml [16.1-70.0] vs. 3.3 [1.8-9.6], P<0.001).The correlations between viral load/ tumor burden and various cytokine levels were shown in Figure 2. Lg viral loads were correlated with lg IL-6 (R2=0.101; P<0.001) and lg IL-10 (R2=0.105; P<0.001) .In CAR-T group, LDH was a common indicator related to tumor burden among patients with ALL, NHL, and MM. The lg LDH concentration was correlated with the lg serum concentration of IL-6 (R2=0.161; P=0.01). The independent risk factors for COVID-19-related sCRS were hypertension history (OR: 7.167, 95% CI: 2.345-21.903; P=0.001) and minimum platelets <100×109 /L during disease course (OR: 9.237, 95% CI: 2.544-33.546; P=0.001). Conclusion: Our study demonstrated that there were similar processes but different intensity of inflammatory responses of sCRS in COVID-19 and CAR-T group. The diagnose and management of COVID-19 related sCRS can learn lessons from treatment of sCRS induced by CAR-T therapy. Keywords: Cytokine release syndrome, COVID-19, Chimeric antigen receptor T-cell therapy Figure 1 Disclosures No relevant conflicts of interest to declare.

scholarly journals Chimeric antigen receptor T cell therapy comes to clinical practice

2019 ◽  
Vol 27 (S2) ◽  
Author(s):  
D. Wall ◽  
J. Krueger
Keyword(s):  
T Cells ◽  
T Cell ◽  
Chimeric Antigen Receptor ◽  
Cellular Therapy ◽  
Lymphoblastic Leukemia ◽  
Antigen Receptor ◽  
Adoptive Cellular Therapy ◽  
T Cell Therapy ◽  
Non Hodgkin Lymphoma ◽  
Car T

Adoptive cellular therapy with chimeric antigen receptor T cells (car-ts) has recently received approval from Health Canada and the U.S. Food and Drug Administration after remarkable and durable remissions were seen in children with recurrent or refractory leukemia and adults with non-Hodgkin lymphoma—responses that were so impressive that a shift in the paradigm of care has now occurred for children with acute lymphoblastic leukemia.    The concept behind car-t immunotherapy is that modification of a patient’s own T cells to facilitate their localization to the cancer cell, with subsequent activation of the T cell effector mechanism and proliferation, will result in targeted killing of cancer cells. The car-ts are a novel drug in that the starting material for the manufacture of the car-t product comes from the patient, whose viable T cells are then genetically modified. Thus, collaboration is needed between the pharmaceutical companies, which must meet good manufacturing standards for each patient’s unique product, and the treating sites. For regulators and health authorities, this new class of drugs requires new paradigms for assessment and approval. Treatments with car-ts require that institutions address unique logistics requirements and management of novel toxicities.    The Hospital for Sick Children has had early experience with both the licensing of clinical trials and the introduction of the first commercial product. Here, we provide an overview of basic concepts and treatment, with caveats drawn from what we have learned thus far in bringing this new therapy to the clinical front line.

CD19 Chimeric Antigen Receptor Therapy for Refractory Aggressive B-Cell Lymphoma

2019 ◽  
Vol 37 (4) ◽  
pp. 328-335 ◽  
Author(s):  
Caron A. Jacobson
Keyword(s):  
B Cell ◽  
Chimeric Antigen Receptor ◽  
Cell Lymphoma ◽  
Rapid Evolution ◽  
Antigen Receptor ◽  
B Cell Lymphoma ◽  
T Cell Therapy ◽  
Non Hodgkin Lymphoma ◽  
Car T Cell Therapy ◽  
Car T

PURPOSE Anti-CD19–directed chimeric antigen receptor (CAR) T-cell therapy has had a resounding effect on the treatment of chemotherapy-insensitive aggressive B-cell non-Hodgkin lymphoma (B-NHL). There are now two US Food and Drug Administration (FDA)–approved products available for treating these patients, and a third product is expected to be approved in the coming months. The question remains: Is there a preferred or best product for my patient? However, answering that question is more complicated than simply balancing the reported efficacy and toxicity results. DESIGN This review outlines potential confounding factors involving the three products and their pivotal clinical trials and highlights additional considerations of manufacturing reliability and overall cost that must be considered when weighing one product against another. It will also review the directions in which the field is moving and strategies being examined to improve efficacy as well as toxicity. CONCLUSION Because a randomized three-arm clinical trial is unlikely, a product may have to be chosen on the basis of results from treatment centers that have experience with all three products. But by the time those results are available, they are likely to be outdated because, given the rapid evolution of the field, the next product will probably have been identified.

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