Toxicity management after chimeric antigen receptor T cell therapy: one size does not fit 'ALL'

Teachey, David T.; Bishop, Michael; Maloney, David G.; Grupp, Stephan A.

doi:10.1038/nrclinonc.2018.19

Cited by 96 publications

(120 citation statements)

References 17 publications

(29 reference statements)

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“…Given the potential severity of both of these complications, there have been significant efforts made in recent years in defining these toxicities and testing potential prevention or treatment modalities, including the formation of toxicity working groups 156 to define cross-institution standards for diagnostic criteria and treatment algorithms. Although significant advances have been made, universal consensus has not been reached, 157 and remains a critical unmet need in the field, especially in the setting of FDA approval, as these therapies move from specialized centers to more broad implementation.…”

Section: Preinfusion Chemotherapymentioning

confidence: 99%

Defining success with cellular therapeutics: the current landscape for clinical end point and toxicity analysis

Kean

2018

Blood

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Cellular therapies play a major and expanding role in the treatment of hematologic diseases. For each of these therapies, a narrow therapeutic window exists, where efficacy is maximized and toxicities minimized. This review focuses on one of the most established cellular therapies, hematopoietic stem cell transplant, and one of the newest cellular therapies, chimeric antigen receptor-T cells. In this review, I will discuss the current state of the field for clinical end point analysis with each of these therapeutics, including their critical toxicities, and focus on the major elements of success for each of these complex treatments for hematologic disease.

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Section: Preinfusion Chemotherapymentioning

confidence: 99%

Defining success with cellular therapeutics: the current landscape for clinical end point and toxicity analysis

Kean

2018

Blood

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“…It also predicts clinical response but does not explain why patients with low grade CRS still have robust and durable responses to CAR‐T cell therapy . Treatment for CRS largely depends on CRS grades, and management of toxicities also varies between adult and pediatric populations . Most patients with grade 1 CRS (fevers, nausea, and myalgia) are managed with supportive care.…”

Section: Introductionmentioning

confidence: 99%

“…With the persistence of fevers or change in clinical status and hypotension, most physicians will begin treatment with tocilizumab, an IL‐6 receptor inhibitor . If no responses are seen to IL‐6 inhibition, corticosteroids are often used and rapidly reverse severe CRS without compromising initial antitumor response …”

Section: Introductionmentioning

confidence: 99%

The acceleration of CAR‐T therapy in non‐Hodgkin lymphoma

Munshi

Ujjani

2018

Hematological Oncology

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Recent advances in diffuse large B‐cell lymphomas have included both identification of high‐risk subtypes characterized by multiply relapsed and/or refractory disease as well as novel treatment in the form of cellular therapy. Chimeric antigen receptor (CAR)‐T cell therapy is a recently developed approach to address the poor outcomes in this patient population. The CAR‐T cell construct has evolved although several iterations as it transitioned from the lab to the clinic. Three major studies have evaluated the efficacy of CD19‐directed CAR‐T cell therapy in aggressive B‐cell non‐Hodgkin lymphoma; each demonstrating durable complete remissions in heavily pretreated patients. The cost of this remarkable therapy, however, includes cytokine release syndrome and neurotoxicity shortly after administration as well as delayed infectious complications due to B‐cell aplasia. Future investigations are focused on the optimizing both safety and efficacy of CAR‐T cell therapy.

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“…Tocilizumab does not seem to affect the efficacy of CAR T-cell therapy in terms of overall response rates, CR rates, or the durability of responses [39, 45, 46]. Siltuximab on the other hand has not been studied as first-line therapy for CRS and is not currently FDA-approved for this indication [42]. Comparative studies are needed to directly compare the effectiveness of tocilizumab and siltuximab in the treatment of CRS.…”

Section: Challengesmentioning

confidence: 99%

“…Patient hospitalization with close monitoring is recommended by Neelapu et al [39] for at least 7–10 days after CAR T-cell infusion. Others have not found this to be necessary in studies using CAR T-cell constructs containing a 4-1BB costimulatory domain, including tisagenlecleucel, in both ALL and NHL populations [42]. …”

Section: Challengesmentioning

confidence: 99%

Chimeric Antigen Receptor T Cells: A Race to Revolutionize Cancer Therapy

Subklewe

Bergwelt‐Baildon

Humpe

2019

Transfus Med Hemother

123

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For years, cancer treatment was dominated by chemotherapy, radiation therapy, and stem cell transplantation. New insights into genetic characteristics of leukemic cells have initiated the development of the chimeric antigen receptor (CAR) T-cell therapy. This type of adoptive cell immunotherapy has been a breakthrough in the treatment of aggressive B-cell lymphoma and B-cell precursor acute lymphoblastic leukemia. In August 2018, the European Commission has approved the first CAR T-cell products – tisagenlecleucel (Kymriah®, Novartis) and axicabtagene ciloleucel (Yescarta®, Gilead) – for hematological neoplasms in Europe. As CAR T cells are a living drug, its benefits can last for many years. The administration of CAR T cells is a complex and costly endeavor involving cell manufacture, shipping of apheresis products, and management of novel and severe adverse reactions. The most common toxicities observed after CAR T-cell therapy are cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome. Current research focuses on improved safety and efficacy in hematological malignancies as well as the translation of CAR T-cell therapy to solid tumors. This review covers the development and current status of CAR T-cell therapy in a clinical setting with focus on challenges and future opportunities.

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Toxicity management after chimeric antigen receptor T cell therapy: one size does not fit 'ALL'

Cited by 96 publications

References 17 publications

Defining success with cellular therapeutics: the current landscape for clinical end point and toxicity analysis

Defining success with cellular therapeutics: the current landscape for clinical end point and toxicity analysis

The acceleration of CAR‐T therapy in non‐Hodgkin lymphoma

Chimeric Antigen Receptor T Cells: A Race to Revolutionize Cancer Therapy

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