Table 5:
General guidelines for initial management of CRS and ICANS in adults.
These general guidelines for initial management of CRS and ICANS (ASTCT grading criteria) for adults are based on our clinical practice at the Fred Hutchinson Cancer Research Center. Practices vary between institutions. Other factors such as co-morbidities, tumor burden, the CAR-T cell product, the cell dose, and kinetics of progression of CRS/ICANS can influence management decisions.
| CRS Grade | Cytokine directed therapy | Corticosteroids | |
|---|---|---|---|
| 1 | Not recommended | Not recommended unless otherwise indicated (e.g. ICANS) | |
| 2 | Clinically stable | Not recommended | Not recommended unless otherwise indicated (e.g. ICANS) |
| Unstable (e.g. requiring increasing fluid support or hypoxic) | Consider tocilizumab 8mg/kg (max 800mg) | If tocilizumab given, recommend dexamethasone 10mg BID x 2 doses then review | |
| 3 | Tocilizumab 8mg/kga | Dexamethasone 10mg BID to QID | |
| 4 | Tocilizumab 8mg/kga Consider other therapies if failure to improvea,b | Dexamethasone 10mg QID; consider methylprednisolone 1g daily x 3 doses if no rapid improvement | |
| ICANS Grade | Cytokine directed therapy | Corticosteroids |
|---|---|---|
| 1 | Not recommended unless otherwise indicated (e.g. CRS) | Not recommended unless otherwise indicated (e.g. CRS) |
| 2 | Not recommended unless otherwise indicated (e.g. CRS) | Consider dexamethasone 10mg BID x 2 doses then review |
| 3 | Not recommended unless otherwise indicated (e.g. CRS) | Dexamethasone 10mg BID to QID |
| 4 | Not recommended unless otherwise indicated (e.g. CRS) Consider other therapies if failure to improvea,b | Dexamethasone 10mg QID; consider methylprednisolone 1g daily x 3 doses |
Note the package insert for axicabtagene ciloleucel states that patients with Grade 2 or higher CRS may receive tocilizumab every 8 hours as needed if not responsive to intravenous fluids or increasing supplemental oxygen; no more than 3 doses in a 24 hour period or a total of 4 doses are recommended [42]. At our institution, we consider using other cytokine directed therapies (e.g. anakinra) if CRS is refractory to 2 doses of tocilizumab.
Other approaches for refractory and life-threatening CRS/ICANS have been considered. However, at this point there is limited data to support efficacy or safety of these approaches (e.g. cytokine-directed therapies, hemofiltration, plasma exchange, IVIG).