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• To enhance your knowledge of chimeric antigen receptor (CAR) T-cell therapy
• To be aware of the potential side effects, adverse reactions and life-threatening acute toxicities associated with CAR T-cell therapy
• To recognise what the role of the nurse may entail in relation to CAR T-cell therapy
Chimeric antigen receptor (CAR) T-cell therapy is a relatively new and innovative immunotherapy for haemato-oncological diseases. In the UK, CAR T-cell therapy can be used to treat some patients with relapsed or refractory acute lymphoblastic leukaemia or diffuse large B-cell lymphoma. However, CAR T-cell therapy can have side effects that have implications for patients’ physical and psychosocial well-being and may induce adverse reactions that can cause life-threatening acute toxicities. Nurses may have a significant role throughout the CAR T-cell therapy process, including in supporting patient decision-making, administering infusions, monitoring patients, identifying and managing adverse reactions, and providing follow-up care. This article provides an overview of CAR T-cell therapy and describes some of its potential side effects and adverse reactions. The authors also consider the role of the nurse and the implications for the nursing workforce in terms of meeting the needs of the increasing numbers of patients who may become eligible for this treatment as it is extended to other cancer types.
Nursing Standard. doi: 10.7748/ns.2024.e12349
Peer reviewThis article has been subject to external double-blind peer review and checked for plagiarism using automated software
Correspondence Conflict of interestNone declared
Thoms E, Simons A (2024) Chimeric antigen receptor (CAR) T-cell therapy: an overview for nurses. Nursing Standard. doi: 10.7748/ns.2024.e12349
Published online: 09 September 2024
Malignant haematological disease, often referred to as blood cancer or liquid tumours, involves a malignant change in the haematopoietic stem cells in the bone marrow, which affects their development and/or function (Hoffbrand and Steensma 2019). Examples of malignant haematological diseases are leukaemia, lymphoma and myeloma (Brown and Cutler 2012). Haematological malignancies are treated with a variety of anti-cancer treatments and the mode of treatment is dependent on many variables, most importantly the location and stage of the disease, the severity of the symptoms and the patient’s general health (Mehta and Hoffbrand 2014). These variables assist healthcare professionals in identifying a patient’s level of function through use of the Eastern Cooperative Oncology Group (ECOG) Performance Status Scale, which is a scoring system used to assess the patient’s fitness to receive treatment for cancer (Oken et al 1982).
Acute lymphoblastic leukaemia (ALL) is a type of malignant haematological disease that affects white blood cells, particularly lymphocytes, in the bone marrow (Brown and Cutler 2012). It can develop rapidly – within days or weeks – and can spread to other parts of the body, such as the lymph nodes, liver, spleen, central nervous system or testicles. ALL can be treated using chemotherapy, corticosteroids and/or growth factors (hormones that encourage cells to divide and develop), radiotherapy, stem cell transplantation and, more recently, immunotherapy (Mehta and Hoffbrand 2014).
Diffuse large B-cell lymphoma (DLBCL) is a malignancy of the lymphatic system (Howard and Hamilton 2013). The lymphatic system, which includes bone marrow, the thymus and lymph nodes, is a vital part of the immune system; the two systems are interlinked and work together to protect the body from infection and help to maintain homeostasis (Mehta and Hoffbrand 2014). Swollen lymph nodes can be a sign of infection, but can also be a sign of malignant haematological disease (Grundy 2006). In DLBCL, the cancerous B-cells (cancerous white blood cells) tend to collect in the lymph nodes or other organs. The disease is usually treated with chemotherapy, radiotherapy and immunotherapy (Hatton et al 2017).
If patients with ALL or DLBCL who are receiving traditional anti-cancer treatments experience relapse (return of the disease), the treatment options are limited (National Institute for Health and Care Excellence (NICE) 2003, 2016). However, extensive research of malignant haematological disease and its treatment has led to the development of a novel immunotherapy, chimeric antigen receptor (CAR) T-cell therapy, which can be used to treat some patients with relapsed or refractory ALL and DLBCL (NICE 2023a, 2023b). The decision about whether a patient is eligible for this treatment is made by the National CAR-T Clinical Panel, which comprises specialists and patient advocates, and the therapy is delivered in a designated treating centre (Cancer Research UK 2024, NHS England 2024).
At the time of writing there is limited evidence on the five-year survival of patients with ALL or DLBCL treated with CAR T-cell therapy, particularly in the UK, since the treatment is still in its infancy and delivered in only 18 designated treating centres (16 in England, one in Wales and one in Scotland). However, more data will become available as CAR T-cell therapy becomes used more widely.
In this article, the authors provide an overview of the CAR T-cell therapy process, describe its potential side effects and adverse reactions, and explain the role of the nurse in providing this treatment. The authors also consider the implications for the nursing workforce as this treatment is extended to patients with other cancer types.
• Extensive research of malignant haematological disease and its treatment has led to the development of chimeric antigen receptor (CAR) T-cell therapy, which is a novel immunotherapy
• CAR T-cell therapy uses the patient’s own T-cells to enhance the body’s response to seek and destroy abnormal cells
• CAR T-cell therapy is delivered to the patient via intravenous infusion over 30 minutes, usually by an experienced nurse during an inpatient stay in a designated treating centre
• The role of nurses in CAR T-cell therapy may include: delivering patient education; administering infusions; monitoring, identifying and managing side effects and adverse reactions; and providing follow-up care and support
T-cells are one type of several white blood cells that have a role in the body’s immune response to infection and disease (Peate and Nair 2016). T-cells have a receptor on their cell surface that enables them to lock on to the tumour antigen (markers found on the surface of the cancerous cells) (Balibegloo et al 2020) (Figure 1). The role of an antigen is to alert the body that a cell is abnormal – in this case cancerous – and that action is needed to destroy it (Sompayrac 2015). Once the T-cell receptor has attached to the tumour antigen it releases cytokines, which are signalling proteins that cause other helper T-cells to come to the site. These helper T-cells then attach to the cancer cell and diffuse it with a protein that induces apoptosis (cell death) (Peate and Nair 2016).
CAR T-cell therapy uses the patient’s own T-cells to enhance the body’s response to seek and destroy abnormal cells (Childers 2023). The patient’s T-cells are extracted through apheresis (the separation of blood components using centrifugal force) and are then genetically modified in a laboratory where chimeric antigen receptor proteins are added (McConville et al 2017). The addition of the chimeric antigen receptors to the patient’s T-cells reprogrammes the T-cells to identify and target the cancerous cells more effectively (Figure 2) by enhancing the function of the T-cell immune response, inducing apoptosis of the abnormal cells (Baer 2021).
Before administration of CAR T-cell therapy, the patient’s level of function will be determined using the ECOG Performance Status Scale, and various tests will be conducted to ensure their fitness to receive the treatment and to minimise the risk of adverse effects (Jain et al 2022). These tests will include an electrocardiogram, echocardiogram, computed tomography scan and various blood tests to assess the patient’s haemoglobin levels, white blood cell count, electrolytes and renal function (Hayden et al 2022). If the patient is deemed well enough to receive the treatment, they may be administered chemotherapy or radiotherapy, referred to as ‘bridging therapy’, to manage the disease in the meantime and to lower the number of T-cells in the body (Hayden et al 2022, Amara 2023).
CAR T-cell therapy is delivered to the patient via intravenous infusion over 30 minutes (Childers 2023). In the UK, this procedure is usually undertaken by an experienced nurse during an inpatient stay in one of the designated treating centres (Cancer Research UK 2024). An overview of the CAR T-cell therapy process is shown in Table 1.
(Adapted from Hayden et al 2022)
Deciding whether to proceed with CAR T-cell therapy can be a major dilemma for patients, who may already be experiencing an impaired quality of life due to the effects of their disease and because they are offered this treatment when other therapies have been unsuccessful (Williams 2024). Quality of life is defined by the World Health Organization (2012) as ‘individuals’ perceptions of their position in life in the context of the culture and value systems in which they live and in relation to their goals, expectations, standards and concerns’. In this context, the assessment of a person’s quality of life extends beyond their health status to include the effects of health conditions on their psychological well-being and everyday life from their perspective.
Patients and their families need to consider the potential adverse physical and psychosocial effects of receiving CAR T-cell therapy (Table 2), as well as the potentially life-threatening acute toxicities associated with it (Halton et al 2017), and weigh these against the potential benefits of the treatment. Such benefits may include improved quality of life and/or disease modification leading to a potential increase in life expectancy (Halton et al 2017). Healthcare professionals, including nurses, can support the decision-making process by providing relevant information.
(Adapted from Macmillan Cancer Support 2021, Cancer Research UK 2024)
One of the risks for patients receiving CAR T-cell therapy is the potential adverse reactions associated with the treatment, which are primarily caused by the action of the T-cells on the immune response process (Anderson and Latchford 2019, Childers 2023). The main adverse reactions and acute toxicities associated with CAR T-cell therapy are summarised in Table 3.
(Adapted from McConville et al 2017, Smith and Venella 2017, Baer 2021, Amara 2023)
To ensure patient safety, there are stringent processes and protocols that must be followed during the CAR T-cell therapy episode of care which are based on the potential adverse reactions and acute toxicities associated with this treatment (Hayden et al 2022). After receiving the infusion, the patient is monitored as an inpatient in the treating centre for side effects and signs and symptoms of adverse reactions to the treatment for 10-14 days (Table 2 and Table 3). If the patient has not experienced any side effects or adverse reactions during this period, they are deemed at low risk of doing so and are discharged from inpatient care (Amara 2023).
Patients can be discharged to their own home providing they live within one hour of the treating centre so that they can return for twice-weekly follow-up appointments as an outpatient for up to 28 days (Smith and Venella 2017, Amara 2023). These follow-up appointments involve a multidisciplinary review, during which the patient is assessed using the ECOG Performance Status Scale and any side effects or adverse reactions are recorded, monitored and treated as required. Follow-up care then continues monthly for the first year following CAR T-cell therapy, then six monthly for 1-2 years, then annually for up to 15 years (Hayden et al 2022).
CAR T-cell therapy can weaken the patient’s immune system for several months following treatment due to the action on the immune response process (Childers 2023). Therefore, patients should be advised to continue to be vigilant in observing for signs and symptoms of infection, for example by taking their temperature daily, while also avoiding people with active infections and crowded places (Smith and Venella 2017).
Nurses caring for patients undergoing CAR-T cell therapy have an integral role, which may include: delivering patient education before and after the treatment; administering CAR T-cell infusions; monitoring, identifying and managing signs and symptoms of side effects and adverse reactions; and providing follow-up care and support (Anderson and Latchford 2019). To undertake this role effectively, nurses need to understand how CAR T-cell therapy works and the pathophysiology of its potential adverse reactions. This can enable them to quickly recognise the signs and symptoms of the associated acute toxicities (Halton et al 2017), and to provide patients and their families with comprehensive information throughout the process, including when they are deciding whether or not to have the treatment (Steinbach et al 2023). Patients who receive CAR T-cell therapy may have multiple physiological and psychosocial needs due to the complexity and potential adverse effects of the treatment, as well as their diagnosis (McConville et al 2017). Therefore, nurses may also need to refer patients to other services, such as counselling or support groups (Smith and Venella 2017, Anderson and Smith 2020).
The management of patients receiving CAR T-cell therapy is undertaken by nurses in the designated treating centres who have completed specific in-house training on systemic anti-cancer therapy and CAR T-cell therapy, and who may have undertaken relevant education accredited by a higher education institution. This is in line with the Career Pathway, Core Cancer Capabilities and Education Framework, which provides clear and concise guidance on the education and knowledge required by different levels of healthcare professionals caring for patients with cancer (Health Education England 2023). In addition to specified education and training, the designated treating centres will have local protocols in place to support safe and effective administration of CAR T-cell infusions (Baer 2021). Such protocols may include the required documentation, patient reviews and escalation procedures, which will differ between treating centres. Some local protocols may include competencies that must be achieved before the nurse can deliver CAR T-cell therapy unsupervised (He et al 2024).
As further progress is made in cancer research, the use of CAR T-cell therapy may be approved for the treatment of more disease groups, which may increase the numbers of patients who will be offered this treatment. This will require an increase in the number of nurses with the appropriate training, skills and competence in the delivery of CAR T-cell therapy and the management of patients receiving this treatment. Therefore, there is a need to invest in the nursing workforce to ensure there is sufficient capacity to provide patients undergoing CAR T-cell therapy with safe and effective care.
In the UK, some patients with relapsed or refractory ALL or DLBCL can be treated with CAR T-cell therapy, a novel immunotherapy. The CAR T-cell therapy process is complex and adverse reactions to the treatment can result in potentially life-threatening toxicities for patients. Nurses have an important role throughout all stages of the CAR T-cell therapy process, including delivering patient information, administering the treatment, identifying and managing signs and symptoms of adverse reactions, and providing follow-up care. CAR T-cell therapy may be extended to patients with other cancer types, so there is a need for investment in education and training for nurses to ensure patients receive safe and effective care.
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