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Management of patients undergoing CAR T-cell therapy
continued from the previous page
History of CNS disease
CNS involvement by malignancy defined as CNS-3 as per NCCN guidelines excluded; however, those with history of effectively treated CNS disease were eligible
Active CNS involvement by malignancy excluded
Subjects with detectable CSF malignant cells, or brain
metastases, or with history of CSF malignant cells or brain metastases excluded
Relative contra indication; individualized risk- benefit assessment required19
Caution required as higher risk of neurological toxicity
ALL: acute lymphoblastic leukemia; DLBCL: diffuse large B-cell lymphoma; NHL: non-Hodgkin lymphoma; EBMT: European Society for Blood and Marrow Transplantation; N/A: not available; SPC: summary of product characteristics; ECOG: Eastern Cooperative Oncology Group; PS: performance status; BCC: basal cell carcinoma;SCC: squamous cell carcinoma; allo-HCT: allogeneic hematopoietic cell transplantation; GvHD: graft-versus-host disease; BiTE: bispecific monoclonal antibodies; CAR: chimeric antigen receptor; HBV: hepatitis B virus; HCV: hepatitis C virus; HIV: human immunodeficiencyvirus;CNS:centralnervoussystem;NCCN:NationalComprehensiveCancerNetwork.
Table 2. The minimum required tests.
Test methods
Disease confirmation
Hematology Bilirubin
AST/ALT
Creatinine clearance
Hepatitis B*
Hepatitis C*
HIV*
Cardiac function
CNS imaging
Lumbar puncture
Fertility
Trials and/or SPC
ANC >1.0x109/L in NHL trials <26-34 μmol/L
<5xULN
Age- and gender-dependent cut-offs for ELIANA trial,
> 60 mL/min/1.73m2 (JULIET)
Active or latent hepatitis B (test within 8 weeks of screening) (ELIANA, JULIET)
Active hepatitis C (test within 8 weeks of screening) (ELIANA, JULIET)
HIV positive test within 8 weeks
of screening - ineligible for CAR T trials
Hemodynamically stable and LVEF >45% confirmed by echocardiogram
or MUGA scan; Patients with cardiac involvement by NHL were excluded from some trials
ZUMA-1 trial required an MRI of the brain to confirm there was no evidence of lymphoma
Patients with active CNS disease were excluded from trials
Females of childbearing potential must have a negative serum or urine pregnancy test within 48 h of infusion (ELIANA)
EBMT recommendations
Histology only for NHL Immunophenotyping for ALL
Hematology
ANC >1.0x109/L
Chemistry
<34 μmol/L; higher limit acceptable (<43 μmol/L) with Gilbert syndrome
<5x ULN > 30 mL/min
Virology
Mandatory in some countries. To be done within 30 days of leukapheresis and results must be available at the time of collection and shipment
Mandatory in some countries.
To be done within 30 days
of leukapheresis and results must be available at the time of collection and shipment
Mandatory in some countries. To be done within 30 days of leukapheresis and results must be available at the time of collection and shipment
Other work-up
LVEF >40%;
assess for pericardial effusion by echocardiography; ECG
MRI not required except in those with a history of CNS disease or current neurological symptoms of concern
Comment
Evidence of adequate bone marrow reserve
No trial data regarding patients outside of these parameters
Attempt to identify causes e.g. active infections Caution is required in patients with CrCl of <60 mL/min
As per national guidelines Serology/molecular testing
As per national guidelines Serology/molecular testing
KymriahTM is using a lentiviral vector whereas YescartaTM uses
a retroviral vector
Work-up of effusions required to identify causes
A baseline MRI can be helpful, should severe neurological toxicities arise
Lumbar puncture not required except in those with a history of CNS disease or current neurological symptoms of concern
Females of childbearing potential Test must be repeated and confirmed negative must have a negative serum or urine within 8 days of the CAR T-cell infusion
pregnancy test
SPC: summary of product characteristics; EBMT: European Society for Blood and Marrow Transplantation; NHL: non-Hodgkin lymphoma; ALL: acute lymphoblastic leukemia; ANC: absolute neu- trophil count; AST: aspartate aminotransferase: ALT: alanine aminotransferase; ULN: upper limit of normal; CrCl: creatinine clearance; HIV: human immunodeficiency virus; CAR: chimeric antigen receptor; LVEF: left ventricular ejection fraction; MUGA: multiple-gated acquisition; MRI: magnetic resonance imaging; CNS: central nervous system. *Leukapheresis material for KymriahTM manu- facturing will not be accepted from patients with a positive test for active hepatitis B virus, hepatitis C virus or HIV (SPC)
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