Clinical care of chimeric antigen receptor T-cell patients and managing immune-related adverse effects in the ambulatory and hospitalized setting: a review

2019 ◽  
Vol 15 (36) ◽  
pp. 4235-4246 ◽  
Author(s):  
Priya Hays ◽  
Caitlin Costello ◽  
Deepak Asudani
Keyword(s):  
T Cell ◽  
Chimeric Antigen Receptor ◽  
Clinical Care ◽  
Antigen Receptor ◽  
Hematologic Malignancies ◽  
Management Approach ◽  
Cytokine Release ◽  
Cytokine Release Syndrome ◽  
Cell Therapies ◽  
Us Fda

Chimeric antigen receptor (CAR) T-cell therapies are increasingly providing options for care of oncology patients with advanced hematologic malignancies, which has led to two US FDA approvals. However, they are often associated with significant immune related adverse events that require prompt management. These toxicities are mainly cytokine release syndrome and neurotoxicity, and can be managed in an appropriate setting when presenting to nononcologists or internists. This paper discusses patient management for these toxicities. A management approach can be determined by the severity of the toxicity. Tocilizumab, a humanized monoclonal antibody, was FDA approved for the treatment of cytokine release syndrome, and corticosteroids may be used. Neurotoxicity is generally managed with supportive care and steroidal therapy.

Management of chimeric antigen receptor T-cell induced cytokine release syndrome: Current and emerging approaches

2021 ◽  
pp. 107815522110392
Author(s):  
Yunjung H Shin ◽  
Xiaofan Tian ◽  
Jiyeon J Park ◽  
Gee Y (Geeny) Kim ◽  
Emily Aboujaoude ◽  
...  
Keyword(s):  
T Cell ◽  
Chimeric Antigen Receptor ◽  
Clinical Investigation ◽  
Antigen Receptor ◽  
Common Adverse Event ◽  
Cytokine Release ◽  
Cytokine Release Syndrome ◽  
Comprehensive Overview ◽  
T Cell Therapy ◽  
First Line Therapy

The most common adverse event associated with chimeric antigen receptor T-cell therapy is cytokine release syndrome, which is characterized by fever, hypoxia, and hypotension in varying degrees of severity. In severe cases, cytokine release syndrome can result in life-threatening symptoms such as multi-organ failure. The widely accepted first-line therapy for cytokine release syndrome management is tocilizumab with or without corticosteroids, but there is very limited guidance on the proper management of patients unresponsive to this regimen. There are emerging strategies that target cytokine release syndrome through novel mechanisms, showing promise in treating or preventing severe cytokine release syndrome. Although further clinical investigation is necessary to assess the applicability of the emerging approaches, these exploratory therapies may shape the future landscape of chimeric antigen receptor T-cell induced cytokine release syndrome management. This review article provides a comprehensive overview of the current and emerging therapies for the management of chimeric antigen receptor T-cell induced cytokine release syndrome, especially cases that are refractory to tocilizumab and steroids.

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 Efficacy-enhanced and cytokine release syndrome-attenuated anti-CD7 universal chimeric antigen receptor-T cell therapy for relapsed/refractory CD7-positive hematological malignancies: A phase I clinical study

2021 ◽  
Author(s):  
He Huang ◽  
Yongxian Hu ◽  
Yali Zhou ◽  
Mingming Zhang ◽  
Houli Zhao ◽  
...  
Keyword(s):  
T Cell ◽  
Chimeric Antigen Receptor ◽  
Objective Response ◽  
Antigen Receptor ◽  
Cytokine Release ◽  
Cytokine Release Syndrome ◽  
Single Chain ◽  
Antitumor Effects ◽  
Car T ◽  
T Cell Malignancies

Abstract Chimeric antigen receptor-T cell (CAR-T) therapy in T cell malignancies faces fratricide, T cell aplasia, and product contamination. Here, we successfully developed a universal anti-CD7 CAR-T product (RD13-01). RD13-01 contains a bbzg-CAR comprising an anti-CD7 single-chain variable fragment, a 4-1BB costimulatory domain, a CD3ζ signaling domain, the intracellular domain of the common γ chain, and a natural killer cell inhibitory molecule (E-cadherin). TRAC, CD7 and HLA-II were disrupted to avoid graft versus host disease (GvHD), fratricide and rejection. Bbzg-CAR-T exerted antitumor effects superior to those of conventional CAR-T, while exhibiting reduced cytokine production. Among 11 evaluable relapsed/refractory (r/r) patients, no dose-limited toxicity, GvHD, immune effector cell-associated neurotoxicity or severe cytokine release syndrome (grade≥3) occurred. Nine (82%) showed objective response. For r/r leukemia and NHL, complete response rates were 75% and 33.3% respectively. Outstanding safety and efficacy of this universal CAR-T product was achieved in CD7+ T cell malignancies.

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