Article
Biochemistry & Molecular Biology
Concetta Rafaniello, Valerio Liguori, Alessia Zinzi, Mario Gaio, Angela Falco, Luigi Di Costanzo, Francesca Gargano, Valentina Trimarco, Mauro Cataldi, Annalisa Capuano
Summary: In this study, 2905 individual case safety reports (ICSRs) were evaluated, showing that approximately 80% of the reported adverse events related to axi-cel were serious, and approximately 20% did not fully resolve or resulted in death. The most frequently reported adverse events were nervous system disorders and immune system disorders, suggesting that axi-cel may be more neurotoxic than other CAR-T-cell therapies.
Review
Immunology
Robert. C. C. Sterner, Rosalie. M. M. Sterner
Summary: CAR-T cell therapy has shown great potential in treating hematological malignancies, but the associated toxicities, such as ICANS, have hindered its widespread use. Understanding the mechanisms and developing solutions for ICANS is crucial for improving the efficacy and safety of CAR-T cell therapy.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Hematology
Olalekan O. Oluwole, Krimo Bouabdallah, Javier Munoz, Sophie De Guibert, Julie M. Vose, Nancy L. Bartlett, Yi Lin, Abhinav Deol, Peter A. McSweeney, Andre H. Goy, Marie Jose Kersten, Caron A. Jacobson, Umar Farooq, Monique C. Minnema, Catherine Thieblemont, John M. Timmerman, Patrick Stiff, Irit Avivi, Dimitrios Tzachanis, Jenny J. Kim, Zahid Bashir, Jeff McLeroy, Yan Zheng, John M. Rossi, Lisa Johnson, Lovely Goyal, Tom van Meerten
Summary: Prophylactic corticosteroids and earlier intervention with corticosteroids and/or tocilizumab resulted in a reduced rate of severe treatment-related toxicities and high response rates in patients with refractory large B-cell lymphoma. The majority of patients did not experience CRS or NEs within 72 hours of axi-cel treatment. Furthermore, 95% of patients achieved objective responses and 80% achieved complete responses in this study.
BRITISH JOURNAL OF HAEMATOLOGY
(2021)
Article
Pharmacology & Pharmacy
Karthik Nath, Kitsada Wudhikarn, Ana Alarcon Tomas, Miguel-Angel Perales
Summary: This review discusses the safety considerations of axicabtagene ciloleucel in patients with large B-cell lymphoma, including the commonly observed immune-mediated toxicities of cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome. Additionally, it reviews CAR T-cell therapy related cytopenias, infection, organ dysfunction, and the recently described hemophagocytic lymphohistiocytosis.
EXPERT OPINION ON DRUG SAFETY
(2023)
Article
Oncology
Allison Grana, Natalia Gut, Kiersten Williams, Joseph Maakaron, Kyle Porter, Basem M. William, Sumithira Vasu, Sam Penza, Jonathan E. Brammer, Ayman Saad, Marcin Puto, Samantha M. Jaglowski, Julianna Roddy
Summary: This retrospective study evaluated the safety events of axicabtagene ciloleucel treatment in heavily pretreated patients with relapsed or refractory diffuse large B-cell lymphoma. Almost all patients experienced cytokine release syndrome and/or neurotoxicity, indicating the need for real-life experience and data to better manage these toxicities specific to CAR-T therapy.
CLINICAL LYMPHOMA MYELOMA & LEUKEMIA
(2021)
Article
Hematology
Megan Melody, Sangeetha Gandhi, Zaid Abdel Rahman, Paula Lengerke-Diaz, Nicole Gannon, Allison Rosenthal, Tuan Truong, Mattia Novo, Eva Brandes, Gina Lange, Breana Estby, Patrick Johnston, Steve Ansell, N. Nora Bennani, Jonas Paludo, Jose Villasboas Bisneto, Ernesto Ayala, Han W. Tun, Hemant S. Murthy, Vivek Roy, James Foran, Januario Castro, Yi Lin, Mohamed A. Kharfan-Dabaja
Summary: This retrospective analysis of 81 patients treated with axi-cel showed that 22.8% had hypoalbuminemia. Results indicated that axi-cel therapy appeared to overcome the adverse prognostic impact of hypoalbuminemia on overall survival and progression-free survival in these patients. Further large multicenter clinical studies are needed to validate these findings.
EUROPEAN JOURNAL OF HAEMATOLOGY
(2021)
Article
Hematology
Timothy J. Porter, Ana Lazarevic, Jamie E. Ziggas, Ephraim Fuchs, Kiryoung Kim, Helen Byrnes, Leo Luznik, Javier Bolanos-Meade, Syed Abbas Ali, Nirali N. Shah, Nina Wagner-Johnston, Tania Jain
Summary: CAR-HLH, a type of haemophagocytic lymphohistiocytosis-like toxicity that occurs following CAR-T cell therapy, is described in three patients in this report. Prompt recognition and initiation of potentially life-saving treatment for CAR-HLH is crucial.
BRITISH JOURNAL OF HAEMATOLOGY
(2022)
Review
Immunology
XiaoQin Wu, XinYue Zhang, RenDe Xun, MengSi Liu, Zhen Sun, JianChao Huang
Summary: This review investigated the efficacy and safety of CAR-T cell therapy in secondary CNS lymphoma patients, concluding that they could benefit from Axi-cel and Tisa-cel treatment with controllable risks. However, the small sample size introduced a high risk of bias and prevented identifying specific patients who could benefit more from CAR-T cell therapy. Further prospective studies with larger samples and longer follow-up periods are recommended.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Immunology
Jiaying Wu, Yang Cao, Qi Zhang, Wanying Liu, Xiaoxi Zhou, Xi Ming, Fankai Meng, Yicheng Zhang, Chunrui Li, Liang Huang, Jia Wei, Miao Zheng, Shangkun Zhang, Tongcun Zhang, Xiaojian Zhu, Na Wang, Jue Wang, Gaoxiang Wang, Jianfeng Zhou, Bo Liu, Yi Xiao
Summary: Salvage therapy with CD19/CD22 CAR T cell infusion alone and in combination with ASCT shows effectiveness in treating some adult patients with refractory or relapsed Burkitt lymphoma.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Emmanuel Bachy, Steven Le Gouill, Roberta Di Blasi, Pierre Sesques, Guillaume Manson, Guillaume Cartron, David Beauvais, Louise Roulin, Francois Xavier Gros, Marie Therese Rubio, Pierre Bories, Jacques Olivier Bay, Cristina Castilla Llorente, Sylvain Choquet, Rene-Olivier Casasnovas, Mohamad Mohty, Stephanie Guidez, Magalie Joris, Michael Loschi, Sylvain Carras, Julie Abraham, Adrien Chauchet, Laurianne Drieu La Rochelle, Benedicte Deau-Fischer, Olivier Hermine, Thomas Gastinne, Jean Jacques Tudesq, Elodie Gat, Florence Broussais, Catherine Thieblemont, Roch Houot, Franck Morschhauser
Summary: This study compared the efficacy and toxicity of Axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tisa-cel) in patients with relapsed/refractory diffuse large B cell lymphoma (DLBCL). The results showed that axi-cel had better overall response rate, complete response rate, progression-free survival, and overall survival compared to tisa-cel. However, axi-cel also had higher frequency of cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome compared to tisa-cel.
Article
Hematology
Mi Kwon, Gloria Iacoboni, Juan Luis Reguera, Lucia Lopez Corral, Rafael Hernani Morales, Valentin Ortiz-Maldonado, Manuel Guerreiro, Ana Carolina Caballero, Maria Luisa Guerra Dominguez, Jose Maria Sanchez Pina, Alberto Mussetti, Juan Manuel Sancho, Mariana Bastos-Oreiro, Eva Catala, Javier Delgado, Hugo Luzardo Henriquez, Jaime Sanz, Maria Calbacho, Rebeca Bailen, Cecilia Carpio, Jose Maria Ribera, Anna Sureda, Javier Briones, Juan Carlos Hernandez-Boluda, Nuria Martinez Cebrian, Jose Luis Diez Martin, Alejandro Martin, Pere Barba
Summary: This retrospective study evaluated the safety and efficacy of Axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tisa-cel) in relapsed/refractory large B-cell lymphoma (LBCL) outside of clinical trials. The results showed that the real-world experience with these CAR-T cell therapies was comparable to the pivotal trial results.
Review
Oncology
Jun Meng, XiaoQin Wu, Zhen Sun, RenDe Xun, MengSi Liu, Rui Hu, JianChao Huang
Summary: This study summarized the efficacy and safety of three CAR-T cell products in treating hematologic malignancies, showing promising results in patients with different pathological subtypes and clinical characteristics, but also highlighting the potential for severe toxicity in certain situations. Additional data on these products are needed to benefit a broader patient population.
FRONTIERS IN ONCOLOGY
(2021)
Review
Cell Biology
Chieh Yang, John Nguyen, Yun Yen
Summary: This article provides a summary of the adverse effects of CAR-T cell therapies, including cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, and CAR T-cell associated HLH. It discusses the pathophysiology, symptoms, grading, and diagnosis systems, as well as management strategies. The article also gives an overview of measures and modifications currently being explored to limit toxicity in CAR-T cells.
JOURNAL OF BIOMEDICAL SCIENCE
(2023)
Review
Emergency Medicine
Brit Long, Michael J. Yoo, William J. Brady, Angela Holian, Amita Sudhir, Michael Gottlieb
Summary: CAR T-cell therapy represents a significant advancement in cancer treatment, but can lead to severe complications such as CRS and ICANS. Early recognition and management of these complications are crucial for patient outcomes.
AMERICAN JOURNAL OF EMERGENCY MEDICINE
(2021)
Review
Immunology
Yuki Kagoya
Summary: Adoptive immunotherapy using CAR-engineered T cells can effectively treat hematologic malignancies, but its efficacy needs improvement. Modulating cytokine signaling in CAR-T cells through genetic engineering is a promising strategy to enhance their therapeutic efficacy, and synthetic biology approaches have been developed for this purpose. However, CAR-T cell-related toxicities, such as cytokine-release syndrome and neurotoxicity, need to be addressed. This review discusses the exploitation of cytokine signaling and therapeutic target molecules to enhance CAR-T cell functions and prevent or alleviate toxicities.
INTERNATIONAL IMMUNOLOGY
(2023)