Safety and efficacy of chimeric antigen receptor (CAR)-T-cell therapy in persons with advanced B-cell cancers and hepatitis B virus-infection

Wang, Ying; Liu, Yang; Tan, Xu; Pan, Bin; Ge, Jian; Qi, Kunming; Cheng, Hai; Cao, Jiang; Shi, Ming; Zhang, Yan; Qiao, Jianlin; Jing, Guangjun; Wang, Xue; Sang, Wei; Xia, Ruixiang; Zhang, Xi; Li, Zhenyu; Gale, Robert Peter; Zheng, Junnian; Zhu, Feng; Xu, Kailin

doi:10.1038/s41375-020-0936-4

Cited by 23 publications

(22 citation statements)

References 9 publications

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“…Chimeric antigen receptor T (CAR-T) cells, which are genetically modified T cells harvested from patients to express special CARs, target tumor cells and can produce remissions again for patients who are resistant to standard therapies (1). CAR-T cell therapy has demonstrated inspiring efficacy in the treatment of B-cell original malignancies and its scope of application is broadening to many other malignancies even to solid cancers (2)(3)(4)(5)(6). Nevertheless, despite its promising efficacy, adverse events such as cytokine-release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), cytopenia and B-cell aplasia have limited the application of CAR-T cell therapy (7).…”

Section: Introductionmentioning

confidence: 99%

Case Report: Local Cytokine Release Syndrome in an Acute Lymphoblastic Leukemia Patient After Treatment With Chimeric Antigen Receptor T-Cell Therapy: A Possible Model, Literature Review and Perspective

et al. 2021

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Chimeric antigen receptor T (CAR-T) cell therapy has achieved remarkable clinical efficacy in treatment of many malignancies especially for B-cell hematologic malignancies. However, the application of CAR-T cells is hampered by potentially adverse events, of which cytokine release syndrome (CRS) is one of the severest and the most studied. Local cytokine-release syndrome (L-CRS) at particular parts of the body has been reported once in a while in B-cell lymphoma or other compartmental tumors. The underlying mechanism of L-CRS is not well understood and the existing reports attempting to illustrate it only involve compartmental tumors, some of which even indicated L-CRS only happens in compartmental tumors. Acute lymphoblastic leukemia (ALL) is systemic and our center treated a B-cell ALL patient who exhibited life threatening dyspnea, L-CRS was under suspicion and the patient was successfully rescued with treatment algorithm of CRS. The case is the firstly reported L-CRS related to systemic malignancies and we tentatively propose a model to illustrate the occurrence and development of L-CRS of systemic malignancies inspired by the case and literature, with emphasis on the new recognition of L-CRS.

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Section: Introductionmentioning

confidence: 99%

Case Report: Local Cytokine Release Syndrome in an Acute Lymphoblastic Leukemia Patient After Treatment With Chimeric Antigen Receptor T-Cell Therapy: A Possible Model, Literature Review and Perspective

et al. 2021

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“…Given the observation of viral reactivation [ 13 , 14 , 15 , 16 , 17 ], and the potential need for CAR-T therapy in the massive patient population with chronic viral infections (e.g., hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV), etc.) [ 19 , 20 , 21 , 22 , 23 ], viral infection is one of the top problems to be addressed in CAR-T cell therapy.…”

Section: Discussionmentioning

confidence: 99%

Cytomegalovirus Retinitis and Retinal Detachment following Chimeric Antigen Receptor T Cell Therapy for Relapsed/Refractory Multiple Myeloma

Wang

et al. 2022

Current Oncology

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Cytomegalovirus (CMV) retinitis is a rare end-organ disease of CMV infection and is a marker of severe immunosuppression, especially in human immunodeficiency virus (HIV)-positive patients. In multiple myeloma (MM) patients, CMV retinitis has been reported in the post-transplant setting, with an incidence lower than 0.2%, and in patients receiving lenalidomide. Here, we describe the first case of CMV retinitis in myeloma patients following B-cell maturation antigen (BCMA)-targeted chimeric antigen receptor T (BCMA CAR-T) cell therapy. In addition to CMV, the patient developed multiple infections including a mouth ulcer, pneumonia, and fungal enteritis. While the complete remission (CR) status of MM was maintained, he regained a visual acuity of 20/1000 after appropriate ophthalmologic treatment. This single case illustrates the potential of BCMA CAR-T therapy to induce profound humoral immunosuppression, and demonstrates an imperative need for an established standard of monitoring and prophylaxis of post-CAR-T infections.

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“…A cohort of 70 patients from China receiving CAR T-cell therapy demonstrated no significant difference in toxicity and response between patients with and without HBV. 45 Herpes viruses CMV, Ebstein Barr virus (EBV) and human herpesvirus 6 (HHV-6) appear to be rare. Data regarding the natural history of CMV and EBV infection after CAR T-cell therapy are non-existent.…”

Section: Viral Infectionsmentioning

confidence: 99%

Infectious complications of CAR T-cell therapy: a clinical update

Stewart

Henden

2021

Therapeutic Advances in Infection

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Chimeric antigen receptor (CAR) T-cell therapy is a revolutionary treatment modality used to treat haematological malignancies. Lymphocytes are engineered to produce CARs directed towards tumour cell antigens. Clinical trials have demonstrated impressive malignancy-related outcomes. Unfortunately, numerous off-target effects can cause toxicity-related adverse events in this population, the main being cytokine release syndrome and immune effector cell neurotoxicity syndrome. This causes significant patient morbidity and poor outcomes. Patients who receive CAR T-cell therapy are also profoundly immunosuppressed and often cytopenic, which is caused by a multitude of patient- and treatment-related factors. Thus, infection-related complications are also common in this group. Indeed, up to one third of patients will suffer a serious bacterial infection in the first 30 days after therapy. Viral respiratory tract infection appears to be the most common during the late phase and can be severe; one patient has died of influenza A infection. Fungal infection and cytomegalovirus (CMV) reactivation appear to be uncommon. Although institutional guidelines on infection-prevention strategies are available, there is a dearth of evidence to support their approach. Future research needs to target important unanswered questions that remain in this patient population in order to improve their short- and long-term outcomes.

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Safety and efficacy of chimeric antigen receptor (CAR)-T-cell therapy in persons with advanced B-cell cancers and hepatitis B virus-infection

Cited by 23 publications

References 9 publications

Case Report: Local Cytokine Release Syndrome in an Acute Lymphoblastic Leukemia Patient After Treatment With Chimeric Antigen Receptor T-Cell Therapy: A Possible Model, Literature Review and Perspective

Case Report: Local Cytokine Release Syndrome in an Acute Lymphoblastic Leukemia Patient After Treatment With Chimeric Antigen Receptor T-Cell Therapy: A Possible Model, Literature Review and Perspective

Cytomegalovirus Retinitis and Retinal Detachment following Chimeric Antigen Receptor T Cell Therapy for Relapsed/Refractory Multiple Myeloma

Infectious complications of CAR T-cell therapy: a clinical update

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