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I. Yakoub-Agha et al.
Tumor lysis syndrome
CAR T-cell therapy can result in the rapid destruction of tumor cells and therapy-associated adverse events includ- ing tumor lysis syndrome.40-42 Standard hospital protocols should apply. Tumor lysis in certain locations (gut, biliary tree, lungs, genitourinary tract) may lead to perforation
and the release of commensal organisms resulting in peri- tonitis.43
Infections
Active infections should be fully treated and under con- trol prior to the administration of LD conditioning and the
Table 6. Checklist and pre-medication before chimeric antigen receptor T-cell infusion.
Active infection
Cardiac arrhythmia not controlled with medical management
Hypotension requiring vasopressor support
New-onset or worsening
of another non-hematologic organ dysfunction ≥ grade 3
Significant worsening of the clinical condition since start of LD
Pre-medication
Concomitant medication
SPC
Reasons to delay treatment: active uncontrolled infection (KymriahTM and YescartaTM)
Reasons to delay treatment: unresolved
SAR (esp. pulmonary reactions, cardiac reactions or hypotension) from preceding chemotherapies (KymriahTM and YescartaTM)
See above
Reasons to delay treatment: significant clinical worsening of leukemia burden or lymphoma following LD chemotherapy (KymriahTM)
‘It is recommended that patients
be pre-medicated with paracetamol and diphenhydramine or another H1 antihistamine within approximately
30 to 60 minutes prior to KymriahTM infusion’ ‘Paracetamol given orally and diphenhydramine or chlorpheniramine intravenous or oral (or equivalent) approximately 1 hour before YescartaTM infusion is recommended’
Corticosteroids should NOT be used prior to or around the time of the infusion except in case of a life-threatening emergency
EBMT recommendations
Contraindication
Cardiologist opinion is required
Contraindication
Work-up is needed to identify the cause
Work-up is needed to identify the cause
As per SPC
As per SPC
Comment
CAR T-cell infusion should be delayed until the infection has been successfully treated or controlled
Specific individualized risk-benefit assessment required
CAR T-cell infusion should be delayed until the hypotension has been fully treated
Specific individualized risk-benefit assessment required
Specific individualized risk-benefit assessment required
SPC: summary of product characteristics; EBMT: European Society for Blood and Marrow Transplantation; CAR: chimeric antigen receptor; SAR: severe adverse reaction; LD: lymphodepletion.
Table 7. Recommendations regarding the first month after chimeric antigen receptor T-cell infusion.
Period
Day 0 to day +14 post-infusion
From hospital discharge to day +28 post-infusion
SPC and protocols
Some protocols require 5-14 days hospitalization after the infusion
Some protocols require that patients be located within 30 to 60 min of the center
EBMT recommendations
Ideally, 14 days hospitalization
Patients must be located within
60 min of the treating unit
or a well-equipped center*
The continuous presence of a caregiver who is educated to recognize
the signs and symptoms of CRS and ICANS is required
Comments
Shorter hospitalization periods
as well as outpatient follow-up are possible in centers that can provide 24/7 contact with immediate availability of specialist inpatient care. Patients must be located within 30 min
of the center
CRS and, in particular, ICANS can occur after the patient has left the hospital.
In addition, life-threatening complications may occur during this period e.g. septic shock in neutropenic patients
SPC:summary of product characteristics;CRS:cytokine release syndrome;ICANS:immune effector cell-associated neurotoxicity syndrome.* Centers competent to manage such complications.
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haematologica | 2020; 105(2)