scholarly journals Hemophagocytic Lymphohistiocytosis/Macrophage-Activation Syndrome (HLH/MAS) Following Treatment with Tisagenlecleucel

2021 ◽  
Author(s):  
Reyes Maria Martin-Rojas ◽  
Ignacio Gomez-Centurion ◽  
Rebeca Bailen ◽  
Mariana Bastos ◽  
Francisco Diaz-Crespo ◽  
...  
Keyword(s):  
T Cell ◽  
Macrophage Activation ◽  
Mortality Rates ◽  
Cytokine Release ◽  
Cytokine Release Syndrome ◽  
Unusual Manifestation ◽  
Car T Cell ◽  
Car T ◽  
Diagnosis Criteria

CAR-T cell related HLH/MAS is an unusual manifestation of severe cytokine release syndrome (CRS) with high mortality rates and a challenging diagnosis. The establishment of specific diagnosis criteria is essential, and the combination of several techniques for CAR-T cell follow-up, allows a more precise management of this complication.

scholarly journals Cytokine release syndrome and neurological event costs in lisocabtagene maraleucel–treated patients in the TRANSCEND NHL 001 trial

2021 ◽  
Vol 5 (6) ◽  
pp. 1695-1705
Author(s):  
Jeremy S. Abramson ◽  
Tanya Siddiqi ◽  
Jacob Garcia ◽  
Christine Dehner ◽  
Yeonhee Kim ◽  
...  
Keyword(s):  
Health Care ◽  
T Cell ◽  
B Cell Lymphoma ◽  
Cytokine Release ◽  
Cytokine Release Syndrome ◽  
System Perspective ◽  
Cell Therapies ◽  
Car T Cell ◽  
Car T ◽  
Grade 3

Abstract Chimeric antigen receptor (CAR) T-cell therapies have demonstrated high response rates in patients with relapsed/refractory large B-cell lymphoma (LBCL); however, these therapies are associated with 2 CAR T cell–specific potentially severe adverse events (AEs): cytokine release syndrome (CRS) and neurological events (NEs). This study estimated the management costs associated with CRS/NEs among patients with relapsed/refractory LBCL using data from the pivotal TRANSCEND NHL 001 trial of lisocabtagene maraleucel, an investigational CD19-directed defined composition CAR T-cell product with a 4-1BB costimulation domain administered at equal target doses of CD8+ and CD4+ CAR+ T cells. This retrospective analysis of patients from TRANSCEND with prospectively identified CRS and/or NE episodes examined relevant trial-observed health care resource utilization (HCRU) associated with toxicity management based on the severity of the event from the health care system perspective. Cost estimates for this analysis were taken from publicly available databases and published literature. Of 268 treated patients as of April 2019, 127 (47.4%) experienced all-grade CRS and/or NEs, which were predominantly grade ≤2 (77.2%). Median total AE management costs ranged from $1930 (grade 1 NE) to $177 343 (concurrent grade ≥3 CRS and NE). Key drivers of cost were facility expenses, including intensive care unit and other inpatient hospitalization lengths of stay. HCRU and costs were significantly greater among patients with grade ≥3 AEs (22.8%). Therefore, CAR T-cell therapies with a low incidence of severe CRS/NEs will likely reduce HCRU and costs associated with managing patients receiving CAR T-cell therapy. This clinical trial was registered at www.clinicaltrials.gov as #NCT02631044.

scholarly journals Preemptive mitigation of CD19 CAR T-cell cytokine release syndrome without attenuation of antileukemic efficacy

Blood ◽  
2019 ◽  
Vol 134 (24) ◽  
pp. 2149-2158 ◽  
Author(s):  
Rebecca A. Gardner ◽  
Francesco Ceppi ◽  
Julie Rivers ◽  
Colleen Annesley ◽  
Corinne Summers ◽  
...  
Keyword(s):  
T Cell ◽  
Acute Lymphocytic Leukemia ◽  
Negative Impact ◽  
Lymphocytic Leukemia ◽  
Cytokine Release ◽  
Cytokine Release Syndrome ◽  
Car T Cell ◽  
Car T ◽  
Antileukemic Effect ◽  
Life Threatening

Gardner et al report that early intervention with tocilizumab and steroids at the first signs of mild cytokine release syndrome (CRS) following CD19 chimeric antigen receptor (CAR) T-cell infusion for B-cell acute lymphocytic leukemia reduces the development of life-threatening severe CRS without having a negative impact on antileukemic effect.

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.

scholarly journals Regulation of CAR T cell-mediated cytokine release syndrome-like toxicity using low molecular weight adapters

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Yong Gu Lee ◽  
Haiyan Chu ◽  
Yingjuan Lu ◽  
Christopher P. Leamon ◽  
Madduri Srinivasarao ◽  
...  
Keyword(s):  
Molecular Weight ◽  
T Cell ◽  
Low Molecular Weight ◽  
Cytokine Release ◽  
Cytokine Release Syndrome ◽  
Car T Cell ◽  
Car T

scholarly journals The model of cytokine release syndrome in CAR T-cell treatment for B-cell non-Hodgkin lymphoma

2020 ◽  
Vol 5 (1) ◽  
Author(s):  
Jianshu Wei ◽  
Yang Liu ◽  
Chunmeng Wang ◽  
Yajing Zhang ◽  
Chuan Tong ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
Hodgkin Lymphoma ◽  
Cytokine Release ◽  
Cytokine Release Syndrome ◽  
Car T Cell ◽  
Non Hodgkin Lymphoma ◽  
Car T

scholarly journals Development of molecular and pharmacological switches for chimeric antigen receptor T cells

2019 ◽  
Vol 8 (1) ◽  
Author(s):  
Bill X. Wu ◽  
No-Joon Song ◽  
Brian P. Riesenberg ◽  
Zihai Li
Keyword(s):  
T Cells ◽  
T Cell ◽  
Chimeric Antigen Receptor ◽  
Intervention Strategy ◽  
Antigen Receptor ◽  
Cytokine Release ◽  
Cytokine Release Syndrome ◽  
Car T Cells ◽  
Car T Cell ◽  
Car T

Abstract The use of chimeric antigen receptor (CAR) T cell technology as a therapeutic strategy for the treatment blood-born human cancers has delivered outstanding clinical efficacy. However, this treatment modality can also be associated with serious adverse events in the form of cytokine release syndrome. While several avenues are being pursued to limit the off-target effects, it is critically important that any intervention strategy has minimal consequences on long term efficacy. A recent study published in Science Translational Medicine by Dr. Hudecek’s group proved that dasatinib, a tyrosine kinase inhibitor, can serve as an on/off switch for CD19-CAR-T cells in preclinical models by limiting toxicities while maintaining therapeutic efficacy. In this editorial, we discuss the recent strategies for generating safer CAR-T cells, and also important questions surrounding the use of dasatinib for emergency intervention of CAR-T cell mediated cytokine release syndrome.

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