scholarly journals Factors Associated with Survival and Severe Cytokine Release Syndrome of Patients with Relapsed/Refractory B-ALL Receiving CD19 CAR-T Cell Therapy

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 9-9
Author(s):  
Xi Li ◽  
Chengxin Luo ◽  
Shuangnian Xu ◽  
Yanni Ma ◽  
Jieping Chen
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Therapy ◽  
Cytokine Release ◽  
Cytokine Release Syndrome ◽  
T Cell Therapy ◽  
Factors Associated ◽  
Car T Cell ◽  
Car T Cell Therapy ◽  
Car T

Background : Chimeric antigen receptor-modified T (CAR-T) cells against CD19 have achieved great therapeutic effect in patients with relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL). However, factors associated with the duration of survival and the occurrence of severe cytokine release syndrome (CRS) after CD19 CAR-T cell therapy have not been fully defined. Patients and Methods: We analyzed 24 patients with relapsed/refractory B-ALL who received CD19 CAR-T cell therapy in a phase Ⅰ/Ⅱ clinical trial (ClinicalTrials.gov, NCT02349698). Infused CAR-T cell characteristics, its expansion kinetics in vivo, patient characteristics and laboratory parameters were analyzed for their correlation with overall survival (OS), progression-free survival (PFS), and the incidence of severe CRS. Results: Sixteen patients achieved complete remission (CR), among which 13 achieved minimal residual disease-negative CR. Patients achieved CR had significantly prolonged OS and PFS compared with those who did not. Multivariable cox regression showed that lower peak of CAR-T cell expansion and the occurrence of severe CRS were significantly associated with both inferior OS and inferior PFS, and higher proportion of effector memory T cells in the infused cells was only significantly associated with inferior PFS. Nineteen patients developed CRS, among which 6 developed severe CRS. Compared patients with mild CRS, patients with severe CRS experienced worse vital sign instability and pancytopenia, higher incidences of coagulation and organ dysfunctions, and higher concentrations of procalcitonin and cytokines. Multivariable logistic regression showed that higher pretreatment disease burden was independent predictor of severe CRS. Conclusions: Clinical and biological factors correlated with survival and severe CRS of refractory/relapsed B-ALL patients receiving CD19 CAR-T cell therapy were identified. These data may be helpful for improving the efficacy of CAR-T cell therapy, facilitating the recognition and early intervention of severe CRS. Disclosures No relevant conflicts of interest to declare.

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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