scholarly journals Gut microbiome modulates cytokine release syndrome and therapeutic response to CAR-T therapy in hematologic malignancies

2021 ◽  
Author(s):  
He Huang ◽  
Yongxian Hu ◽  
Jingjing Li ◽  
Fang Ni ◽  
Zhongli Yang ◽  
...  
Keyword(s):  
Gut Microbiome ◽  
Hematologic Malignancies ◽  
Lymphocytic Leukemia ◽  
Cytokine Release ◽  
Cytokine Release Syndrome ◽  
T Cell Therapy ◽  
Non Hodgkin Lymphoma ◽  
Car T Cell Therapy ◽  
Car T

Abstract Chimeric antigen receptor (CAR)-T cell therapy has emerged as a promising immunotherapeutic treatment for hematologic malignancies. By comparing the diversity and composition of the gut microbiome during different stages of CAR-T therapy, significant changes were detected, not only in patients with relapsed/refractory multiple myeloma (MM; n = 43), but also in those with acute lymphocytic leukemia (ALL; n = 23) and non-Hodgkin lymphoma (NHL; n = 12). Analysis of treatment responses revealed significant temporal differences in diversity and abundance of Bifidobacterium, Prevotella, Sutterella, and Collinsella between MM patients in complete remission (n = 24) and those in partial remission (n = 11). Furthermore, we found that patients with severe cytokine release syndrome (CRS) exhibited higher abundance of Bifidobacterium, Leuconostoc, Stenotrophomonas, and Staphylococcus. This study has important implications for understanding the biological role of the microbiome in the CAR-T treatment of patients with hematologic malignancies (ChiCTR1800017404).

scholarly journals CAR T-Cell Associated Neurotoxicity: Mechanisms, Clinicopathologic Correlates, and Future Directions

2019 ◽  
Vol 111 (7) ◽  
pp. 646-654 ◽  
Author(s):  
Bradley D Hunter ◽  
Caron A Jacobson
Keyword(s):  
T Cell ◽  
Cell Therapy ◽  
Hematologic Malignancies ◽  
Cytokine Release ◽  
Cytokine Release Syndrome ◽  
T Cell Therapy ◽  
Car T Cell ◽  
Treatment And Prevention ◽  
Car T Cell Therapy ◽  
Car T

AbstractChimeric antigen receptor (CAR) T-cell therapy is a revolutionary new form of immunotherapy for the treatment of hematologic malignancies. The two primary toxicities associated with CAR T-cell therapy include cytokine-release syndrome and neurotoxicity. Cytokine-release syndrome is generally self-limited but high-grade toxicities like hypotension and hypoxemia can be managed with agents that block the effects of IL-6, like tocilizumab, and/or corticosteroids. Although CAR T-cell therapy–associated neurotoxicity is a well-described clinical phenomenon, its pathophysiology remains inadequately understood; treatments and preventive strategies remain elusive. Animal models and clinical trial experience suggest the centrality of monocytes, endothelial dysfunction, and the blood-brain barrier in the development of CAR T-cell–associated neurotoxicity. Here we report what is known from preclinical models, clinical trials, and histopathologic studies regarding the pathophysiology of neurotoxicity, predictors of its incidence, and potential targets for the treatment and prevention of neurotoxicity.

scholarly journals Potential role of Interferon-y inhibition in refractory cytokine release syndrome associated with CAR T-cell therapy

2021 ◽  
pp. bloodcandisc.0203.2021
Author(s):  
Kevin O McNerney ◽  
Amanda M DiNofia ◽  
David T. Teachey ◽  
Stephan A Grupp ◽  
Shannon L Maude
Keyword(s):  
T Cell ◽  
Cell Therapy ◽  
Potential Role ◽  
Cytokine Release ◽  
Cytokine Release Syndrome ◽  
T Cell Therapy ◽  
Car T Cell ◽  
Car T Cell Therapy ◽  
Car T

scholarly journals Clinical Presentation, Management and Biomarkers of Cytokine Release Syndrome after Anti-CD19 CART-Cell Therapy for r/r ALL

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5625-5625
Author(s):  
Ping Li ◽  
Lili Zhou ◽  
Shiguang Ye ◽  
Shaoguang Li ◽  
Aibin Liang
Keyword(s):  
T Cell ◽  
Cell Therapy ◽  
Clinical Presentation ◽  
Cytokine Release ◽  
Cytokine Release Syndrome ◽  
T Cell Therapy ◽  
Car T Cell ◽  
Car T Cell Therapy ◽  
Car T ◽  
Grade 3

Chimeric antigen receptor T (CAR-T) cell therapy has emerged as a novel treatment modality for B-cell malignancies. CD19-specific CAR-T cells induce high rates of initial response among patients with relapsed B-cell acute lymphoblastic leukemia (ALL). However, cytokine release syndrome (CRS) is the most common and severe toxicities of CAR T-cell therapy for ALL, and clinical experience is limited. Here, we describe the clinical presentation and management of 30 patients who presented with CRS following CAR-T cell therapy for relapsed/refractory ALL at our hospital. 12 of the 30 patients (40%) developed grade 1-2 CRS, 14 patients (46.7%) presented with grade 3-4 CRS and 2 patients (6.7%) died of grade 5 CRS. Compared with grade 1-2 CRS, grade 3-4 CRS correlated negatively with overall survival and progression-free survival (P =0.02). We found that higher ferritin levels and percentages of CD19 positive cells in blood lymphocytes cells at time of CAR-T cell infusion were associated with more severe CRS. Grade 3-4 neurotoxicity was frequently present in patients with grade ≧3 CRS. We also observed that the organ disfunctions occurred in sequence after fever onset during the period of CRS. Neurotoxicity, cardiovascular disfunction and cytopenia in some patients manifest as biphasic. Compared to use of tocilizumab for CRS ≧ grade 3, early intervention of tocilizumab for hyperpyrexia duration ≧ 6h alleviates the severity of CRS, and no patients died of severe CRS since this management approach was performed. As use of novel CAR-T cell therapy expands, the data from our clinical experience may help others anticipated the clinical course of organ function and manage CRS in CAR-T therapy. Figure Disclosures No relevant conflicts of interest to declare.

Management of cytokine release syndrome and neurotoxicity in chimeric antigen receptor (CAR) T cell therapy

2019 ◽  
Vol 12 (3) ◽  
pp. 195-205 ◽  
Author(s):  
Utkarsh H. Acharya ◽  
Tejaswini Dhawale ◽  
Seongseok Yun ◽  
Caron A. Jacobson ◽  
Julio C. Chavez ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Therapy ◽  
Chimeric Antigen Receptor ◽  
Antigen Receptor ◽  
Cytokine Release ◽  
Cytokine Release Syndrome ◽  
T Cell Therapy ◽  
Car T Cell ◽  
Car T Cell Therapy ◽  
Car T
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