The chimeric antigen receptor-intensive care unit (CAR-ICU) initiative: Surveying intensive care unit practices in the management of CAR T-cell associated toxicities

Gutiérrez, Cristina; Brown, Anne Rain; Herr, Megan M.; Kadri, Sameer S; Hill, Brian T.; Rajendram, Prabalini; Duggal, Abhijit; Turtle, Cameron J.; Patel, Kevin; Lin, Yi; May, Heather; Moraes, Alice Gallo De; Maus, Marcela V.; Frigault, Mathew J.; Brudno, Jennifer N.; Athale, Janhavi; Shah, Nirali N.; Kochenderfer, James N.; Dharshan, Ananda; Beitinjaneh, Amer; Arias, Alejandro; McEvoy, Colleen; Mead, Elena; Stephens, Robert S.; Nates, Joseph L.; Neelapu, Sattva S.; Pastores, Stephen M.

doi:10.1016/j.jcrc.2020.04.008

Cited by 36 publications

(37 citation statements)

References 40 publications

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“…75 Although initial studies reported reduced expansion and lacking persistence of CAR T cells in patients who received corticosteroids, 3 early steroid use in subsequent studies has not been associated with detrimental effects on clinical remission rates or CAR T cell persistence. 76,77 With regards to the choice of the corticosteroid agent, dexamethasone at a dosage of 10 mg every 6-8 h or methylprednisolone at a dose of 1-2 mg/kg BW are most commonly used, 78 with dexamethasone being preferred in case of concomitant neurotoxicity due to superior central nervous system (CNS) penetration and improvement of the integrity of the BBB. [79][80][81][82] After resolution of hypotension and hypoxia, tapering of corticosteroids should be carried out based on the patient's individual response.…”

Section: Management Of Crsmentioning

confidence: 99%

“…Regarding vasopressors, norepinephrine has been most widely used as first-line adrenergic agonist for hemodynamic support in CRS patients. 78 However, catecholamine feedback loops may contribute to maintenance of CRS in affected patients, 84 raising the question of whether non-adrenergic vasopressors such as vasopressin might be more beneficial than adrenergic agonists in this setting. Due to common new-onset cardiac dysfunction in patients with high-grade CRS, 85,86 cardiac monitoring, including regular echocardiograms, is advised.…”

Section: Management Of Crsmentioning

confidence: 99%

“…36 Anakinra has been used at a dosage of 2-8 mg/kg BW/day via subcutaneous administration 47 and might be most effective when used early in the course of CRS or even as prophylactic agent, given that IL-1 has shown to precede IL-6 production. 36 Despite reports of clinical use of siltuximab and anakinra, 8,78,87,119 systematic evaluation of both agents is pending.…”

Section: Crs and Icans Refractory To Tocilizumab And/or Corticosteroidsmentioning

confidence: 99%

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Side-effect management of chimeric antigen receptor (CAR) T-cell therapy

et al. 2021

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Chimeric antigen receptor (CAR) T cells directed against the B-cell marker CD19 are currently changing the landscape for treatment of patients with refractory and/or relapsed B-cell malignancies. Due to the nature of CAR T cells as living drugs, they display a unique toxicity profile. As CAR T-cell therapy is extending towards other diseases and being more broadly employed in hematology and oncology, optimal management strategies of side-effects associated with CAR T-cell therapy are of high relevance. Cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), and cytopenias constitute challenges in the treatment of patients with CAR T cells. This review summarizes the current understanding of CAR T-cell toxicity and its management.

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Section: Management Of Crsmentioning

confidence: 99%

Section: Management Of Crsmentioning

confidence: 99%

Section: Crs and Icans Refractory To Tocilizumab And/or Corticosteroidsmentioning

confidence: 99%

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Side-effect management of chimeric antigen receptor (CAR) T-cell therapy

et al. 2021

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“…Although the acute symptoms of toxicities such as CRS and ICANS are generally reversible, they are associated with significant morbidity and up to 47% of patients may require admission to an intensive care unit (ICU) ( 12 ). Joint recommendations from the Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network-Stem Cell Transplantation and Cancer Immunotherapy (SCT-CI) Subgroup and MD Anderson CARTOX working committees were developed to diagnose and manage these complications in younger patients, improve safety, and standardize monitoring ( 10 ).…”

Section: Introductionmentioning

confidence: 99%

Immune Effector Cell Associated Neurotoxicity (ICANS) in Pediatric and Young Adult Patients Following Chimeric Antigen Receptor (CAR) T-Cell Therapy: Can We Optimize Early Diagnosis?

et al. 2021

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The Cornell Assessment for Pediatric Delirium (CAPD) was first proposed by the Pediatric Acute Lung Injury and Sepsis Investigators Network-Stem Cell Transplantation and Cancer Immunotherapy Subgroup and MD Anderson CARTOX joint working committees, for detection of immune effector cell associated neurotoxicity (ICANS) in pediatric patients receiving chimeric antigen receptor (CAR) T-cell therapy. It was subsequently adopted by the American Society for Transplantation and Cellular Therapy. The utility of CAPD as a screening tool for early diagnosis of ICANS has not been fully characterized. We conducted a retrospective study of pediatric and young adult patients (n=15) receiving standard-of-care CAR T-cell products. Cytokine release syndrome (CRS) and ICANS occurred in 87% and 40% of patients, respectively. ICANS was associated with significantly higher peaks of serum ferritin. A change in CAPD from a prior baseline was noted in 60% of patients with ICANS, 24–72 h prior to diagnosis of ICANS. The median change from baseline to maximum CAPD score of patients who developed ICANS versus those who did not was 13 versus 3, respectively (p=0.0004). Changes in CAPD score from baseline may be the earliest indicator of ICANS among pediatric and young adult patients which may warrant closer monitoring, with more frequent CAPD assessments.

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“…With regard to the treatment of NT, tocilizumab has limited efficacy due to its difficulty in penetrating the BBB and even increasing the CSF IL-6 level because of the peripheral blockade of IL-6R ( 94 , 159 ). For this reason, some agencies regard corticosteroids, such as dexamethasone, as the first-line therapy for NT ( 160 ), but the thresholds for administration and dosing schemes vary and have not been prospectively compared. On the other hand, CAR engineering strategies to overcome CRS and NT have been proposed, including “on/off” switch systems, suicide gene systems and direct antagonism approaches ( 161 , 162 ).…”

Section: Clinical Strategiesmentioning

confidence: 99%

Challenges and Clinical Strategies of CAR T-Cell Therapy for Acute Lymphoblastic Leukemia: Overview and Developments

Huang

Xiao

et al. 2021

Front. Immunol.

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Chimeric antigen receptor (CAR) T-cell therapy exhibits desirable and robust efficacy in patients with acute lymphoblastic leukemia (ALL). Stimulated by the revolutionized progress in the use of FDA-approved CD19 CAR T cells, novel agents with CAR designs and targets are being produced in pursuit of superior performance. However, on the path from bench to bedside, new challenges emerge. Accessibility is considered the initial barrier to the transformation of this patient-specific product into a commercially available product. To ensure infusion safety, profound comprehension of adverse events and proactive intervention are required. Additionally, resistance and relapse are the most critical and intractable issues in CAR T-cell therapy for ALL, thus precluding its further development. Understanding the limitations through up-to-date insights and characterizing multiple strategies will be critical to leverage CAR T-cell therapy flexibly for use in clinical situations. Herein, we provide an overview of the application of CAR T-cell therapy in ALL, emphasizing the main challenges and potential clinical strategies in an effort to promote a standardized set of treatment paradigms for ALL.

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The chimeric antigen receptor-intensive care unit (CAR-ICU) initiative: Surveying intensive care unit practices in the management of CAR T-cell associated toxicities

Cited by 36 publications

References 40 publications

Side-effect management of chimeric antigen receptor (CAR) T-cell therapy

Side-effect management of chimeric antigen receptor (CAR) T-cell therapy

Immune Effector Cell Associated Neurotoxicity (ICANS) in Pediatric and Young Adult Patients Following Chimeric Antigen Receptor (CAR) T-Cell Therapy: Can We Optimize Early Diagnosis?

Challenges and Clinical Strategies of CAR T-Cell Therapy for Acute Lymphoblastic Leukemia: Overview and Developments

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