CAR T-cell therapy and critical care

Messmer, Anna S.; Que, Yok-Ai; Schankin, Christoph; Banz, Yara; Bacher, Ulrike; Novak, Urban; Pabst, Thomas

doi:10.1007/s00508-021-01948-2

Cited by 29 publications

(24 citation statements)

References 56 publications

(138 reference statements)

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“…CAR-T-cell therapy is a highly promising therapeutic option in the treatment of advanced lymphoproliferative neoplasms such as diffuse large B-cell lymphoma (DLBCL), acute lymphatic leukemia (ALL), and mantle cell lymphoma [ 1 , 2 , 3 , 4 ]. CD19-directed CAR-T-cells have an impact on malignant B-cell tissues as well as the healthy B-cell compartment and thus lead to B-cell depletion and hypogammaglobulinemia [ 5 , 6 ]. Frequent complications are Cytokine release syndrome (CRS) in more than 60% and CAR-T-Related Encephalopathy Syndrome (CRES) in more than 30% of the patients, according to the literature [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

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Humoral Responses to Repetitive Doses of COVID-19 mRNA Vaccines in Patients with CAR-T-Cell Therapy

Gössi

Bacher

Haslebacher

et al. 2022

Cancers

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Background: Due to B-cell aplasia following CAR-T-cell therapy, patients are at risk of severe SARS-CoV-2 course. Methods: COVID-19 vaccines were assessed by IgG antibody tests against SARS-CoV-2 spike protein (anti-S1/S2). Vaccination procedures: group (1): CAR-T-cells followed by two to four vaccine doses; group (2): Two vaccine doses prior to CAR-T-cells, followed by doses 3 or 4. Results: In group 1 (n = 32), 7/30 patients (23.2%) had positive antibody tests after a second dose, 9/23 (39.1%) after a third dose, and 3/3 patients after a fourth dose. A third dose led to seroconversion in 5 of 21 patients (23.8%) with available data, while a fourth dose did so in 2/3 patients. Higher B-cells (AUC: 96.2%, CI: 89–100, p = 0.0006) and lower CAR-T-cell copies (AUC: 77.3%, CI: 57–97, p = 0.0438) were predictive of positive humoral vaccine response. In group 2 (n = 14), 6/14 patients (42.9%) had a positive antibody test after a second dose, 3/8 patients (37.5%) after a third dose, and 3/4 patients after a fourth dose. A third dose led to seroconversion in 1/8 patients (12.5%), while a fourth dose did so in 3/4 patients. Conclusion: Additional vaccine doses increased seroconversion rates whilst high B-cell counts and low CAR-T-cell copy numbers were associated with positive antibody response.

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Section: Introductionmentioning

confidence: 99%

“…Increased serum IL-6 levels and clinical CRS symptoms can contribute to the indication of therapeutic interventions [ 8 ]. Tocilizumab should be administered to patients with CRS, while corticosteroids are used in patients with CRES and CRS not responsive to tocilizumab [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

Humoral Responses to Repetitive Doses of COVID-19 mRNA Vaccines in Patients with CAR-T-Cell Therapy

Gössi

Bacher

Haslebacher

et al. 2022

Cancers

Self Cite

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“…In the UK, issues of communication between primary and secondary care settings have long been recognised [ 85 ], and are further complicated by the short-term provision of CAR-T care via tertiary or quaternary services [ 86 ]. These issues are particularly apparent when patients with rare conditions present in primary care [ 87 ] or emergency departments [ 88 ]. Empowering patients offers one solution [ 89 ] but not all patients are comfortable assuming a more active role [ 90 ] and improving lines of communication between specialists and colleagues involved in managing complex patients remains a pressing issue [ 91 ] though is not intractable for all ATMPs as demonstrated by the role of primary care in gene therapies in the United States [ 92 ].…”

Section: Discussionmentioning

confidence: 99%

“I just wanted to speak to someone- and there was no one…”: using Burden of Treatment Theory to understand the impact of a novel ATMP on early recipients

Litchfield

Calvert

Kinsella

et al. 2023

Orphanet J Rare Dis

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Background Advanced therapy medicinal products such as Chimeric antigen receptor T-cell therapy offer ground-breaking opportunities for the treatment of various cancers, inherited diseases, and chronic conditions. With development of these novel therapies continuing to increase it’s important to learn from the experiences of patients who were among the first recipients of ATMPs. In this way we can improve the clinical and psychosocial support offered to early patient recipients in the future to support the successful completion of treatments and trials. Study design We conducted a qualitative investigation informed by the principles of the key informant technique to capture the experience of some of the first patients to experience CAR-T therapy in the UK. A directed content analysis was used to populate a theoretical framework informed by Burden of Treatment Theory to determine the lessons that can be learnt in supporting their care, support, and ongoing self-management. Results A total of five key informants were interviewed. Their experiences were described within the three domains of the burden of treatment framework; (1) The health care tasks delegated to patients, Participants described the frequency of follow-up and the resources involved, the esoteric nature of the information provided by clinicians; (2) Exacerbating factors of the treatment, which notably included the lack of understanding of the clinical impacts of the treatment in the broader health service, and the lack of a peer network to support patient understanding; (3) Consequences of the treatment, in which they described the anxiety induced by the process surrounding their selection for treatment, and the feeling of loneliness and isolation at being amongst the very first recipients. Conclusions If ATMPs are to be successfully introduced at the rates forecast, then it is important that the burden placed on early recipients is minimised. We have discovered how they can feel emotionally isolated, clinically vulnerable, and structurally unsupported by a disparate and pressured health service. We recommend that where possible, structured peer support be put in place alongside signposting to additional information that includes the planned pattern of follow-up, and the management of discharged patients would ideally accommodate individual circumstances and preferences to minimize the burden of treatment.

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“…Although CAR immune cell therapy has significant potential as a viable therapeutic method, it has potentially life-threatening side effects and safety problems in clinical applications [ 221 , 222 , 223 ] (Fig. 3 ).…”

Section: Limitations and Challengesmentioning

confidence: 99%

Recent findings on chimeric antigen receptor (CAR)-engineered immune cell therapy in solid tumors and hematological malignancies

et al. 2022

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Advancements in adoptive cell therapy over the last four decades have revealed various new therapeutic strategies, such as chimeric antigen receptors (CARs), which are dedicated immune cells that are engineered and administered to eliminate cancer cells. In this context, CAR T-cells have shown significant promise in the treatment of hematological malignancies. However, many obstacles limit the efficacy of CAR T-cell therapy in both solid tumors and hematological malignancies. Consequently, CAR-NK and CAR-M cell therapies have recently emerged as novel therapeutic options for addressing the challenges associated with CAR T-cell therapies. Currently, many CAR immune cell trials are underway in various human malignancies around the world to improve antitumor activity and reduce the toxicity of CAR immune cell therapy. This review will describe the comprehensive literature of recent findings on CAR immune cell therapy in a wide range of human malignancies, as well as the challenges that have emerged in recent years.

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CAR T-cell therapy and critical care

Cited by 29 publications

References 56 publications

Humoral Responses to Repetitive Doses of COVID-19 mRNA Vaccines in Patients with CAR-T-Cell Therapy

Humoral Responses to Repetitive Doses of COVID-19 mRNA Vaccines in Patients with CAR-T-Cell Therapy

“I just wanted to speak to someone- and there was no one…”: using Burden of Treatment Theory to understand the impact of a novel ATMP on early recipients

Recent findings on chimeric antigen receptor (CAR)-engineered immune cell therapy in solid tumors and hematological malignancies

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