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I. Yakoub-Agha et al.
Figure 2. Management of chimeric antigen receptor T-cell-related neurological toxicity. Adapted from Cornillon et al.62 ICE. Immune effector cell-associated encephalopathy; CAPD: Cornell Assessment of Pediatric Delirium; EEG: electroencephalography; ICU: intensive care unit; IV: intravenous; ICANS: effector cell-associ- ated neurotoxicity syndrome; MRI: magnetic resonance imaging; LP: lumbar puncture; CRS: cytokine release syndrome; IL1R: interleukin-1 receptor; IL-6: interleukin 6.
linemia. There are also more theoretical concerns about the risk of secondary malignancies and both neurological and autoimmune diseases.
It should be recognized that all patients will have been treated previously with multiple anti-cancer therapies, some having also undergone allogeneic HCT. Some patients may receive CAR T-cell treatment at overseas centers and may then return to a CAR T-cell therapy or HCT center. There is a duty-of-care on all CAR T-cell- administering centers to arrange for appropriate local fol- low-up. In cases of geographical transition, formal com- munication, including discharge correspondence and other clinical material such as imaging files, should be provided to new healthcare providers.
Protocols and policies (standard operating procedures) for long-term follow-up will need to be put in place. These should cover shared care and out-reach arrangements and should be based on service level agreements between CAR T-cell centers and referring centers.
Multidisciplinary teams dealing with CAR T-cell thera- pies should arrange for long-term follow-up of treated patients in order to capture disease status and the late effects of CAR T-cell and prior treatments. The multidisci- plinary team should include a physician with responsibil-
ity for CAR T-cell administration, disease-specific special- ists, long-term follow-up nursing staff, data managers and clinical trial staff.
Long-term follow-up clinics may be incorporated into local arrangements for generic allogeneic HCT ‘late effects’ clinics with other allogeneic HCT patients, although dedi- cated clinics for the late effects of CAR T-cell therapy can be developed if a critical mass of survivors is reached.
The clinic should systematically monitor for the follow- ing outcomes: (i) disease status – remission, minimal resid- ual disease, relapse, management of relapse, death, (ii) fur- ther treatments administered after CAR T-cell therapy, including allogeneic HCT and other immune effector cell therapy/Advanced Therapy Medicinal Products; (iii) late effects – for stable patients in ongoing remission, 3- monthly monitoring for the first year, annually thereafter or as clinically appropriate; (iv) infections, (v) immunolog- ical status – cell markers, immunoglobulins, including CAR T-cell persistence; (vi) new cancers, including sec- ondary myeloid diseases; (vii) new autoimmunity and autoimmune diseases; (viii) endocrine, reproductive and bone health (including growth and development in chil- dren and young adult patients); (ix) neurological status (including recovery from ICANS); (x) psychological status
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haematologica | 2020; 105(2)