Fast Facts: CAR T-Cell Therapy in Diffuse Large B-Cell Lymphoma

A practical resource for nurses

R.J. Buka, D. Moloney

• Editorial: S. Karger
• Año: 2021
• ISBN:
  9783318069358
• Categoría: Medicine
• Categoría: Hematology

Diffuse large B-cell lymphoma (DLBCL) is the most common form of high-grade non-Hodgkin lymphoma. While treatment with immunochemotherapy has generally shown good outcomes, specific subgroups of patients with high-risk disease have an unfavorable prognosis. Extensive efforts have been made to improve outcomes in these patients. As such, CD19-targeted chimeric antigen receptor (CAR) T-cell therapy has become the new standard of care for patients with relapsed or refractory DLBCL after at least two prior lines of therapy. It is an exciting new therapeutic intervention that is integral to the concept of personalized medicine. Table of Contents: • DLBCL: an overview • CAR T cells • CAR T-cell products • Delivering CAR T-cell therapy and managing patient expectations • CAR T-cell therapy-related toxicities

4	Delivering CAR T-cell therapy and managing patient expectations

All healthcare professionals involved with the care and management of patients receiving CAR T-cell therapy have an important role in supporting and educating patients and their caregivers through each stage of their treatment, the key steps of which are shown below (Figure 4.1).

•Eligibility evaluation

•Leukapheresis

•Bridging therapy (if required)

•Lymphodepleting chemotherapy

•Infusion and monitoring

•Long-term follow-up

Figure 4.1 The patient pathway for autologous CAR T-cell therapy.

Where possible, specialist psychological support, palliative care for symptom control and support from allied healthcare professionals should be made available before, during and after treatment.

Patient eligibility

Not all patients with relapsed or refractory DLBCL after two lines of therapy are eligible for CAR T-cell therapy. The benefits must be carefully examined for each individual patient by a multidisciplinary team. Most CAR T-cell treatment centers have a multidisciplinary team of hematology and/or oncology physicians, histopathologists, specialist nurses, pharmacists, social workers, cell-therapy coordinators and other key decision makers who review both disease-related morbidity/mortality and patient-related factors, including psychological stability and logistical requirements, alongside alternative treatment options before making the final decision on provision of CAR T-cell therapy (Table 4.1).¹ In some countries, health insurance obligations also need to be addressed before assessment and treatment can proceed.

TABLE 4.1

Eligibility parameters and factors to consider for CAR T-cell therapy^*

•Confirmation of CD19-positive status†

•No response to, or relapse after, ≥ 2 prior lines of treatment for DLBCL

•Ineligible for autologous or allogeneic HSCT

•Disease status

– Low tumor burden and extranodal involvement

– No active CNS involvement

– Lymphocyte count (> 0.1 × 10⁹/L)

– Other hematologic parameters (e.g. ANC > 1.0 × 10⁹/L)^*

•No active infection (active infections must be discussed with the hematology consultants and relevant manufacturing companies)

•Assessment of comorbidities

•Viral (and other infections) status: HIV, HBV, HCV (and HTLV and syphilis in Europe [not USA])

•Renal, lung, hepatic and cardiac function

– SpO₂ > 92% without oxygen

– Ejection fraction ≥ 40%^* (and no evidence of pericardial effusion within 180 days^‡)

– ALT/AST < 5 × ULN^*

– Bilirubin < 34 μmol/L^*

– Creatinine clearance > 30 mL/min/1.73m^2*

•Patient’s performance status (ECOG 0–2)§

•Baseline imaging (may be useful in the event of neurological toxicities)

•Negative pregnancy test for women of childbearing potential

•Patient’s recovery from previous treatment

•Psychosocial evaluation^**

•Level of caregiver support^**

•Logistics of treatment

– Availability of treatment in the area where the patient lives, or ability to travel

– Practicalities of travel and accommodation

– Financial considerations

^*Parameters for eligibility differ between treatment centers. Cut-off values are based on EBMT recommendations.

^†Confirmed using flow cytometry or immunohistochemical staining. This is important, particularly if the patient has already been treated with a CD19-targeted agent (e.g. blinatumomab).

^‡Provided the subject has not received an anthracycline-based treatment or experienced a cardiac event or change in performance status.

§Real-world data with axicabtagene ciloleucel includes patients with ECOG PS > 2.

^**Psychological complications and lack of caregiver support will not exclude patients from CAR T-cell treatment, but these patients may require additional support from specialist services or extended family members/friends.

ALT, alanine aminotransferase; ANC, absolute neutrophil count; AST, aspartate aminotransferase; ECOG, Eastern Cooperative Oncology Group; HBV/HCV, hepatitis B/C virus; HTLV, human T-cell lymphotropic virus.

Excluding a patient from CAR T-cell therapy requires very careful consideration, particularly as the reasoning will need to be fully explained to the patient and their family. Typical exclusion criteria for CAR T-cell therapy (for patients in whom it is otherwise indicated) are CNS involvement, rapid disease progression, major frailty due to comorbidities, thrombocytopenia and active infections (including hepatitis B and C). Patients with prior hepatitis B or C are eligible but should have a negative PCR test result. HIV infection is not necessarily a contraindication. Ideally, patients will not have received prior treatment with therapies such as bendamustine that harm the viability of harvested T cells² but, again, this is not an absolute contraindication.

The criteria on which to base the exclusion of a patient from CAR T-cell therapy can be absolute or more nuanced, the latter being based on a holistic patient assessment that weighs up the regulatory approvals, benefits and risks of treatment, likelihood of success and availability of funding. As well as carefully considering whether the treatment is in the patient’s best interest,³ the ethical principal of social justice must be considered, as healthcare providers have a responsibility to rationally allocate finite resources.

Finally, the disease needs to be managed while CAR T cells are being manufactured. Given the time this can take (see below), clinical stability before embarking on CAR T-cell therapy is an important consideration.

Patient selection for commercial CAR T-cell therapy differs in the USA, EU and UK. In the USA, individual CAR T-cell centers are responsible for suitable patient selection, whereas in the EU the process depends on the member state. In the UK, once a patient has been identified as a candidate for one of the commercial CAR T-cell products, individual centers present the case to an external body of experts, nominated by national authorities, for final approval – unless the patient has private health insurance that will cover the cost.

Managing patient expectations

There has been a lot of coverage about CAR T-cell therapy and its successes in the media and on social media, so patients may have preconceptions about the treatment and its outcomes. While early data are promising (see Chapter 3), patients need to be aware there is no guarantee the treatment will work. Results from real-world data have indicated that approximately 40–55% of people treated with CAR T-cell therapy will achieve a complete response, but comprehensive data beyond 4 years are not yet available.^4–6

Key aspects of communication

Eligible patients and their caregivers need to be given a realistic picture of what to expect before treatment starts, including a clear explanation of what CAR T cells are and a frank discussion about:

•the benefits versus the risks of CAR T-cell therapy

•how long the treatment process will take and the steps involved

•what venous access/central venous access may be required

•the possibility of CAR T-cell manufacturing failure

•the likely side effects, their severity and possible admission to ICU

•possible outcomes of treatment

•how long the patient will need to stay in hospital

•the level of caregiver support required (availability and proximity to treatment center)

•the practicalities of travel and accommodation during treatment

•the need for long-term (lifetime) follow-up

•the unknown long-term side effects, given the lack of long-term follow-up data

•the cost (if applicable).

Clear, frank discussions. Patients need to be given a clear explanation of the treatment process and the timelines involved (see below). They need to be well informed about the risks, including the complications of leukapheresis and lymphodepleting chemotherapy (see below) and the potentially life-threatening toxicities of CAR T-cell therapy (see Chapter 5).

When it comes to discussing outcomes, health professionals must be frank about the expected response. Patients must be given time to digest information about the whole CAR T-cell treatment process, and the information provided must be presented at a level that the patient can understand. It is important that patients are aware they will be monitored for adverse reactions and the reoccurrence of disease for years after treatment.

Psychological and emotional support are important for both the patient and their caregivers when preparing for, during and after CAR T-cell therapy. Although there is limited research, feedback from patient-reported outcomes questionnaires has shown that patients experience increasing anxiety throughout the CAR T-cell therapy process (from before lymphodepleting treatment to 90 days after CAR T-cell infusion), which is slow to alleviate even if they respond to treatment.⁷ Specific fears reported by patients before CAR T-cell therapy include the anxiety of having cells collected, the severity of expected side effects, the potential need for intensive care, the possibility of the treatment not working, the unknown recovery times from side effects and the possibility of relapse after an initial response within the first year.⁸

In the authors’ experience, patient...