Table 1.
Recommendations for general screening and eligibility before CT (adapted from Hayden et al., 2022).39,∗
| Criterion | EBMT/EHA recommendations∗ | AD-specific recommendations |
|---|---|---|
| Performance status | ECOG <2, Karnofsky >60% or Lansky >60% | Same as hematological indications for all CTs (MSC, CART, Tregs) in ADs |
| Prior treatments, including prior immunosuppressive treatment | Relative contraindication. Any systemic immunosuppressive treatment may impair the efficacy of CART. |
Consider balance of active disease, sequelae, damage and the possibility of withdrawing immunosuppressive therapies in the time window required to perform CTs. Specific wash out periods for CART cell process are described in table 10. |
| Infections | Active infection is a contraindication. In most cases, active infection requires only a temporary deferral. Nasopharyngeal PCR for SARS-CoV-2 before CT should be negative. Treatment should be delayed in cases of positive COVID-19 PCR.41 Some latent infections e.g., HIV, are a contraindication to manufacturing for several (but not all) commercial and trial CART products. When proceeding to CART in cases of latent HBV, HCV or HIV infections, prophylactic anti-viral treatment is required. |
Same as hematological indications for all CTs (MSC, CART, Tregs) in ADs |
| CNS involvement | EBMT recommendations consider risk/benefit ratio. Anticonvulsant prophylaxis is mandatory in CNS involvement when using CART cell approaches. |
There is no evidence suggesting substantially increased ICANS risk in AD patients receiving CART cells. However CNS involvement and peripheral neuropathy should be assessed at baseline and individual patient risk has to be considered, especially in CART. |
| Disease confirmation | Diagnosis should be confirmed using appropriate tests. | Activity, damage and organ involvement should be carefully assessed before CTs in ADs. |
| Bilirubin AST/ALT |
<34 mmol/l in trials; higher limit acceptable (<43 mmol/l) with Gilbert's syndrome. <4 ULN a contraindication in some trials. |
Specific AD involvement should be ruled out before CTs. |
| Creatinine clearance | >30 ml/min. | Same as hematological indications for all CTs (MSC, CART, Tregs) in ADs. |
| Hepatitis B and C | As per national guidelines Serology/molecular testing. |
Same as hematological indications for all CTs (MSC, CART, Tregs) in ADs. |
| HIV | Leukapheresis for some CART cells as mentioned in SPC (e.g., tisagenlecleucel [Kymriah] manufacturing) will not be accepted from patients with a positive test for active HBV, HCV or HIV. | Same as hematological indications for all CTs (MSC, CART, Tregs) in ADs. |
| Cardiac function | TTE to assess cardiac function and exclude significant pericardial effusions and structural abnormalities. LVEF <40% (via 4D EF or Simpson's biplane method) is a relative contraindication. ECG to exclude significant arrhythmias. Cardiac biomarkers (troponin and NT-proBNP) at baseline. CMR to assess extent of disease with cardiac involvement. |
Extensive cardiac function assessment is mandatory in AD patients undergoing CTs (MSC, CART, Tregs). |
| CNS imaging and lumbar puncture | MRI not required except in those with a history of CNS disease or current neurological symptoms. Lumbar puncture not required except in those with a history of CNS disease or current neurological symptoms |
In case of underlying diagnosis of SLE and neurological ADs, a detailed clinical examination, Montreal Cognitive Assessment (MOCA),42 MRI ± EEG are strongly recommended. |
| Fertility | Females of childbearing potential must have a negative serum or urine pregnancy test. Test must be repeated and confirmed negative within 8 days of the CART cell infusion |
Same as hematological indications for all CTs (MSC, CART, Tregs) in ADs. Fertility assessment and preservation should be proposed to AD patients before a CT. |
Abbreviations: AD autoimmune diseases; Chimeric Antigen Receptors T cells (CART); CMR cardiovascular magnetic resonance; CNS central nervous system; COVID-19 Coronavirus disease 2019; CT cellular therapy; EBMT European Society for Blood and Marrow Transplantation; ECG electrocardiogram; EEG electroencephalogram; EHA European Hematology Association; HBV Hepatitis B virus; HCV Hepatitis C virus; HIV Human immunodeficiency virus; ICANS immune effector cell-associated neurotoxicity syndrome; LVEF left ventricular ejection fraction; MRI magnetic resonance imaging; MSC mesenchymal stromal cells; NT-proBNP N-terminal pro-brain natriuretic peptide; PCR polymerase chain reaction; SARS-CoV-2 severe acute respiratory syndrome coronavirus 2; SLE systemic lupus erythematosus; SPC summary of Product Characteristics; TTE transthoracic echocardiogram; Tregs regulatory T cells.
These EBMT recommendations were made for CART in hematologic malignancies and may differ to ADs.