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Curated Papers > Recent research on high-impact "CAR-T therapy" (IF≥30, last 5 years)

Critical care management of chimeric antigen receptor T-cell therapy recipients. ​

Literature Information ​

DOI10.3322/caac.21702
PMID34613616
JournalCA: a cancer journal for clinicians
Impact Factor232.4
JCR QuartileQ1
Publication Year2022
Times Cited40
Keywordschimeric antigen receptor (CAR) T cells, critical care, immune-oncology, lymphoblastic leukemia-lymphoma, non-Hodgkin lymphoma
Literature TypeJournal Article, Review
ISSN0007-9235
Pages78-93
Issue72(1)
AuthorsAlexander Shimabukuro-Vornhagen, Boris Böll, Peter Schellongowski, Sandrine Valade, Victoria Metaxa, Elie Azoulay, Michael von Bergwelt-Baildon

TL;DR ​

This review discusses the advancements and clinical applications of chimeric antigen receptor (CAR) T-cell therapy, which has significantly improved treatment outcomes for hematologic malignancies, particularly in relapsed acute lymphoblastic leukemia and lymphoma. However, it also highlights the severe toxicities associated with this therapy, emphasizing the need for effective management strategies and addressing the challenges to enhance patient safety.

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chimeric antigen receptor (CAR) T cells · critical care · immune-oncology · lymphoblastic leukemia-lymphoma · non-Hodgkin lymphoma

Abstract ​

Chimeric antigen receptor (CAR) T-cell therapy is a promising immunotherapeutic treatment concept that is changing the treatment approach to hematologic malignancies. The development of CAR T-cell therapy represents a prime example for the successful bench-to-bedside translation of advances in immunology and cellular therapy into clinical practice. The currently available CAR T-cell products have shown high response rates and long-term remissions in patients with relapsed/refractory acute lymphoblastic leukemia and relapsed/refractory lymphoma. However, CAR T-cell therapy can induce severe life-threatening toxicities such as cytokine release syndrome, neurotoxicity, or infection, which require rapid and aggressive medical treatment in the intensive care unit setting. In this review, the authors provide an overview of the state-of-the-art in the clinical management of severe life-threatening events in CAR T-cell recipients. Furthermore, key challenges that have to be overcome to maximize the safety of CAR T cells are discussed.

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Primary Questions Addressed ​

  1. What are the specific protocols in place for managing cytokine release syndrome in CAR T-cell therapy recipients?
  2. How does the management of neurotoxicity differ from other toxicities associated with CAR T-cell therapy?
  3. What role does early intervention play in improving outcomes for patients experiencing severe toxicities after CAR T-cell therapy?
  4. Are there particular patient populations that are more susceptible to the severe toxicities of CAR T-cell therapy, and how should their management differ?
  5. What advancements in supportive care are being explored to enhance the safety and efficacy of CAR T-cell therapy in critical care settings?

Key Findings ​

1. Research Background and Objectives: Chimeric antigen receptor (CAR) T-cell therapy represents a groundbreaking advancement in the treatment of hematologic malignancies, particularly for patients with relapsed or refractory acute lymphoblastic leukemia and lymphoma. The therapy exemplifies the successful translation of basic immunological research into clinical applications. However, the aggressive nature of CAR T-cell therapy can lead to severe toxicities, such as cytokine release syndrome and neurotoxicity, which necessitate prompt and effective management in critical care settings. This review aims to provide a comprehensive overview of the current strategies employed in the critical care management of CAR T-cell therapy recipients, highlighting the severe complications that can arise and the necessary interventions to mitigate such risks.

2. Main Methods and Findings: The authors conducted a thorough literature review to summarize the current state of clinical management for CAR T-cell therapy recipients facing life-threatening complications. They outlined the common toxicities associated with CAR T-cell therapy, emphasizing the need for rapid identification and treatment within an intensive care unit (ICU) environment. The findings indicate that while CAR T-cell products demonstrate high efficacy in inducing remission, their associated toxicities pose significant challenges that require immediate and aggressive interventions. The review discusses various management protocols, including the use of tocilizumab for cytokine release syndrome and supportive care measures for neurotoxicity and infection.

3. Core Conclusions: The review underscores that while CAR T-cell therapy has transformed treatment possibilities for certain hematologic cancers, the management of its severe toxicities remains a critical challenge. Effective critical care management strategies are essential to optimize patient outcomes and enhance the safety profile of CAR T-cell therapy. The authors conclude that the development of standardized treatment protocols and the establishment of dedicated ICU resources are vital for the successful management of CAR T-cell therapy complications.

4. Research Significance and Impact: This review is significant as it highlights the dual nature of CAR T-cell therapy—its potential for life-saving outcomes juxtaposed with the risk of severe toxicity. By addressing the challenges in critical care management, the authors contribute to the ongoing discourse on improving the safety and efficacy of CAR T-cell therapy. The insights drawn from this review can inform clinical practice, guide future research, and ultimately enhance patient care strategies in the context of advanced immunotherapy. The emphasis on developing robust management protocols is crucial for healthcare providers, as it can lead to improved survival rates and quality of life for patients undergoing this innovative treatment.

Literatures Citing This Work ​

  1. Comparison of Droplet Digital PCR and Metagenomic Next-Generation Sequencing Methods for the Detection of Human Herpesvirus 6B Infection Using Cell-Free DNA from Patients Receiving CAR-T and Hematopoietic Stem Cell Transplantation. - Jiao Meng;Hongyan Ji;Liting Chen;Aichun Liu - Infection and drug resistance (2022)
  2. Progress on CAR-T cell therapy for hematological malignancies. - Kejia Hu;Yue Huang;Yongxian Hu;He Huang - Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences (2022)
  3. The Economic Burden of CAR T Cell Therapies Ciltacabtagene Autoleucel and Idecabtagene Vicleucel for the Treatment of Adult Patients with Relapsed or Refractory Multiple Myeloma in the US. - Buthainah Ghanem;Lu Shi - BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy (2022)
  4. Interferon with Dogma in Cytokine Release Syndrome and Acute Lung Injury. - Scott J Denstaedt;Rachel L Zemans - American journal of respiratory cell and molecular biology (2023)
  5. Acute Kidney Injury in Cancer Immunotherapy Recipients. - Adrien Joseph;Antoine Lafarge;Elie Azoulay;Lara Zafrani - Cells (2022)
  6. Progresses, Challenges, and Prospects of CRISPR/Cas9 Gene-Editing in Glioma Studies. - Xianhui Kang;Yijian Wang;Pan Liu;Baojun Huang;Baofeng Zhou;Shufang Lu;Wujun Geng;Hongli Tang - Cancers (2023)
  7. GPR116 receptor regulates the antitumor function of NK cells via Gαq/HIF1α/NF-κB signaling pathway as a potential immune checkpoint. - Dandan Guo;Chenxu Jin;Yaoxin Gao;Haizhen Lin;Li Zhang;Ying Zhou;Jie Yao;Yixin Duan;Yaojun Ren;Xinhui Hui;Yujia Ge;Renzheng Yang;Wenzheng Jiang - Cell & bioscience (2023)
  8. A novel DNA methylation-related gene signature for the prediction of overall survival and immune characteristics of ovarian cancer patients. - Sixue Wang;Jie Fu;Xiaoling Fang - Journal of ovarian research (2023)
  9. Thermoresponsive Polypeptide Fused L-Asparaginase with Mitigated Immunogenicity and Enhanced Efficacy in Treating Hematologic Malignancies. - Sanke Zhang;Yuanzi Sun;Longshuai Zhang;Fan Zhang;Weiping Gao - Advanced science (Weinheim, Baden-Wurttemberg, Germany) (2023)
  10. Multidisciplinary recommendations for the management of CAR-T recipients in the post-COVID-19 pandemic era. - Tingting Zhang;Weiwei Tian;Shuang Wei;Xinyi Lu;Jing An;Shaolong He;Jie Zhao;Zhilin Gao;Li Li;Ke Lian;Qiang Zhou;Huilai Zhang;Liang Wang;Liping Su;Huicong Kang;Ting Niu;Ailin Zhao;Jing Pan;Qingqing Cai;Zhenshu Xu;Wenming Chen;Hongmei Jing;Peng Li;Wanhong Zhao;Yang Cao;Jianqing Mi;Tao Chen;Yuan Chen;Ping Zou;Veronika Lukacs-Kornek;Christian Kurts;Jian Li;Xiansheng Liu;Qi Mei;Yicheng Zhang;Jia Wei - Experimental hematology & oncology (2023)

... (30 more literatures)

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