Corticosteroids do not influence the efficacy and kinetics of CAR-T cells for B-cell acute lymphoblastic leukemia

Liu, Shuangyou; Deng, Biping; Yin, Zhichao; Pan, Jing; Lin, Yuehui; Ling, Zhuojun; Wu, Tong; Dong, Chen; Chang, Alex H.; Gao, Zhiyong; Song, Yanzhi; Zhao, Yuliang; Tong, Chunrong

doi:10.1038/s41408-020-0280-y

Cited by 122 publications

(74 citation statements)

References 16 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%

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%

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

et al. 2021

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“…Other drugs, such as siltuximab (an IL-6 blocker) ( 153 ), anakinra (an IL-1 receptor blocker) ( 154 ), and dasatinib (a tyrosine kinase inhibitor) ( 155 ), have been applied in clinical trials with significant effectiveness. For the administration of corticosteroids, their impact on CAR T-cell activity remains controversial ( 156 , 157 ). When corticosteroids are used, the dose should be controlled and individualized according to the patient’s response.…”

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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“…For patients with an unsatisfactory response, second line relies on systemic corticosteroids. In this regard, recent data showed that early therapeutic intervention at the first signs of CRS -including the use of corticosteroids -can prevent serious complications without affecting clinical results, mitigating the fear that these drugs could hamper CAR T-cell efficacy (59,60). Although in some centers corticosteroids are now commenced early, possibly at the same time as tocilizumab (61), the aforementioned results might not be valid for all CAR T-cell products, and the best dose and duration of corticosteroids treatment remains to be defined.…”

Section: Car T-cell Toxicity Cytokine Release Syndrome Diagnosis and mentioning

confidence: 99%

The Advent of CAR T-Cell Therapy for Lymphoproliferative Neoplasms: Integrating Research Into Clinical Practice

et al. 2020

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Research on CAR T cells has achieved enormous progress in recent years. After the impressive results obtained in relapsed and refractory B-cell acute lymphoblastic leukemia and aggressive B-cell lymphomas, two constructs, tisagenlecleucel and axicabtagene ciloleucel, were approved by FDA. The role of CAR T cells in the treatment of B-cell disorders, however, is rapidly evolving. Ongoing clinical trials aim at comparing CAR T cells with standard treatment options and at evaluating their efficacy earlier in the disease course. The use of CAR T cells is still limited by the risk of relevant toxicities, most commonly cytokine release syndrome and neurotoxicity, whose management has nonetheless significantly improved. Some patients do not respond or relapse after treatment, either because of poor CAR T-cell expansion, lack of anti-tumor effects or after the loss of the target antigen on tumor cells. Investigators are trying to overcome these hurdles in many ways: by testing constructs which target different and/or multiple antigens or by improving CAR T-cell structure with additional functions and synergistic molecules. Alternative cell sources including allogeneic products (off-the-shelf CAR T cells), NK cells, and T cells obtained from induced pluripotent stem cells are also considered. Several trials are exploring the curative potential of CAR T cells in other malignancies, and recent data on multiple myeloma and chronic lymphocytic leukemia are encouraging. Given the likely expansion of CAR T-cell indications and their wider availability over time, more and more highly specialized clinical centers, with dedicated clinical units, will be required. Overall, the costs of these cell therapies will also play a role in the sustainability of many health care systems. This review will focus on the major clinical trials of CAR T cells in B-cell malignancies, including those leading to the first Cerrano et al. CART Research and Clinical Practice FDA approvals, and on the new settings in which these constructs are being tested. Besides, the most promising approaches to improve CAR T-cell efficacy and early data on alternative cell sources will be reviewed. Finally, we will discuss the challenges and the opportunities that are emerging with the advent of CAR T cells into clinical routine.

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Corticosteroids do not influence the efficacy and kinetics of CAR-T cells for B-cell acute lymphoblastic leukemia

Cited by 122 publications

References 16 publications

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

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

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

The Advent of CAR T-Cell Therapy for Lymphoproliferative Neoplasms: Integrating Research Into Clinical Practice

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