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Management of patients undergoing CAR T-cell therapy
cytomegalovirus, human herpes virus-6 or Epstein-Barr viremia, Clostridium difficile colitis, cholangitis, and viral encephalitis.67,72-74
Nursing and psychological support of patients
CAR T cells are generally being administered in a small number of regional specialist centers to which patients are referred from general hospitals. Patients who are treated with CAR T cells may therefore experience high levels of anxiety due to their new environment as well as their prognosis. Many will be socially isolated and at a signifi- cant distance from their established support networks. The role of the clinical nurse specialist is vital to the suc- cess of the procedure as well as providing essential bed- side support. Referral to local counselling/psychology services should be offered to these patients when appro- priate.
Patients who are being treated on an outpatient basis and their caregivers should receive comprehensive educa- tion on the symptoms of CRS and neurotoxicity and patients should attend the treating hospital without delay in the event that they begin to feel unwell. On discharge, they should be instructed to remain within 1 hour’s travel of the treating hospital for at least 4 weeks following the infusion, during which time a caregiver should always be present. If the patient lives further away, then alternative accommodation, such as a local hotel or apartment, will be required. Independently of whether the patient is living at home or lodging in a local apartment, ambulatory care arrangements for rapid re-admission should be well estab- lished.
All patients must be informed of the potential risks and the precautions that they need to take, as described in the relevant product patient information leaflet. They may also receive further written information, according to local practice, in the form of a patient information booklet or leaflet. This should include information and education on the symptoms of CRS and serious neurological adverse reactions, the need to report any symptoms immediately to their treating physician and the need to remain in close proximity to the center in which the CAR T cells were administered for at least 4 weeks following the infusion.
Patients must be advised to keep their Patient Advice Card with them at all times and to show it to any health- care professional they encounter, especially if they are admitted to another hospital. Patients are advised not to drive for 8 weeks after the infusion and only after resolu- tion of any neurological symptoms. This is due to the risk of delayed neurological toxicity. It is also preferable to have a responsible adult such as a parent, spouse or other caregiver available during the first 3 months following the infusion. A reliable, consistent and well-informed caregiv- er is essential.
Long-term follow-up from day +100 onwards –
‘late effects’
Little is known about the long-term effects of CAR T- cell therapy. Only a small cohort of patients has been fol- lowed for more than 2 years. The main identified compli- cations are prolonged cytopenias and hypogammaglobu-
Table 12. Recommended minimum frequency of attendance at centers for monitoring for late effects after chimeric antigen receptor T-cell ther- apy.
Post CAR-T
Day +100 to 1 year One year to 15 years
Stable patients
Three-monthly Annually
Complications
As clinically indicated
Disease monitoring
Frequency of visits required is disease-specific and monitoring could be performed by CAR T-cell center or referring clinician
Comment
Patients who proceed to subsequent allo-HCT, cytotoxic therapy and/or immune effector cell therapy should be followed as per Majhail et al. 201275
Comment
No longer required following
normalization
Testing for CAR T-cell persistence is not standard. Checking for B-cell depletion as a surrogate marker is an option
CAR: chimeric antigen receptor; allo-HCT: allogeneic hematopoietic cell transplantation
Table 13. Recommended tests to be performed at long-term follow-up clinics.
Test
Full blood count, biochemistry panel
Viral infection (PB PCR, NPA)
Quantitative immunoglobulins
± serum protein electrophoresis
Peripheral blood immunophenotyping
– CD3/4/8/16+56/19*
CAR T-cell monitoring where kits are available for routine monitoring
of anti-CD19 CAR T*
Endocrine function and other standard late effects testing appropriate to age
Purpose
Standard follow-up
Viral reactivation Immune reconstitution
Immune reconstitution
CAR T-cell persistence
Standard follow-up
Frequency
At every visit
As clinically indicated At every visit
Every second visit
Every visit. However, no longer required when absent for two consecutive tests
As clinically indicated
PB: peripheral blood; PCR: polymerase chain reaction; NPA: naso-pharyngeal aspirate; CAR: chimeric antigen receptor. *Equivalent test methods for other immune effector cells as they become available
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