Background
Clinical Manifestations
- Fever, hypotension, tachypnea, tachycardia, headache, rash, dyspnea, hypoxemia
- With BiTE, most common after first dose or first few doses
- Time of onset is variable
- CAR-T: 2-3 days (range 1 to 14 days)
- Haploidentical HSCT: 1 to 3 days
- Bispecific antibodies: usually within 24-48 hours (range from minutes up to 9 days)
Prognosis
- Usually resolves within a few days to a few weeks
ASTCT CRS Grading1
| Parameter | Grade 1 | Grade 1 | Grade 3 | Grade 4 |
|---|---|---|---|---|
| Fever | ≥38ºC | ≥38ºC | ≥38ºC | ≥38ºC |
| with | ||||
| Hypotension | — | Not on vasopressors | One vasopressor ± vasopressin | Multiple vasopressors |
| and/or | ||||
| Hypoxia | — | Low-flow nasal cannula | High-flow nasal cannula, facemask, nonrebreather mask, Venturi mask | Positive-pressure ventilation (non-invasive or invasive) |
Management
- Broad-spectrum antibiotics empirically
- Grade 1: supportive care; if persistent fever for 72 hours consider tocilizumab
- Grade 2-4:
- Tocilizumab 8 mg/kg (max 800 mg), can be repeated q8h up to 4 doses; plus
- Dexamethasone 10 mg IV q12h (Grade 2) or q6h (Grades 3 & 4)
References
- ^ Daniel W. Lee, Bianca D. Santomasso, Frederick L. Locke, Armin Ghobadi, Cameron J. Turtle, Jennifer N. Brudno, Marcela V. Maus, Jae H. Park, Elena Mead, Steven Pavletic, William Y. Go, Lamis Eldjerou, Rebecca A. Gardner, Noelle Frey, Kevin J. Curran, Karl Peggs, Marcelo Pasquini, John F. DiPersio, Marcel R.M. van den Brink, Krishna V. Komanduri, Stephan A. Grupp, Sattva S. Neelapu. ASTCT Consensus Grading for Cytokine Release Syndrome and Neurologic Toxicity Associated with Immune Effector Cells. Biology of Blood and Marrow Transplantation. 2019;25(4):625-638. doi:10.1016/j.bbmt.2018.12.758.
