Record to update:
Adverse Occurrence type:
MPHO Type:
Estimates Frequency:
Two most common toxicities attributable to CAR T-cell therapy are CRS (cytokine release syndrome) and ICANS (immune effector cell‐associated neurotoxicity syndrome). The frequency of these toxicities strongly depend on the patient population and the type of CAR T-cell product used. However, it is safe to say that CRS is more common than ICANS.
Time to detection:
CRS and ICANS are observed acutely after CAR T-cell infusion (<2 weeks). ICANS typically occurs after CRS has subsided.
Alerting signals, symptoms, evidence of occurrence :
The CRS manifests with a noninfectious flulike syndrome. The onset of the cytokine release syndrome correlates with the pharmacokinetic characteristics of the CAR T cells, with a temporal association between the syndrome and peak levels of CAR T-cells. On the other hand, ICANS typically presents as a toxic encephalopathy with word‐finding difficulty, aphasia, and confusion but can progress in more severe cases to depressed level of consciousness, coma, seizures, motor weakness, and cerebral edema.
Demonstration of imputability or root cause:
The onset of CRS correlates with the pharmacokinetic characteristics of the CAR T cells, with a temporal association between the syndrome and peak levels of CAR T-cells. Also, CRS is an on-target toxic effect and is not common in patients who do not have a clinical response after CAR therapy. The pathophysiology of ICANS is less well understood than CRS. Like CRS, cytokines, chemokines, and degree of CAR T‐cell expansion have been associated with severity of neurotoxicity.
Imputability grade:
3 Definite/Certain/Proven
Groups audience:
Note:
This is the secondary review for item #1972.
Suggest new keywords:
Cytokine Release Syndrome
Immune Effector Cell‐Associated Neurotoxicity Syndrome
Adverse occurrence description:
CAR T (Toxic Effects Associated with CAR T Cells)
Suggest references:
Neelapu, SS. Managing the toxicities of CAR T‐cell therapy. Hematological Oncology. 2019; 37( S1): 48– 52. https://doi.org/10.1002/hon.2595
Expert comments for publication:
The article by Carl H. June and Michel Sadelain gives a short overview of CAR T-cell therapy (the CAR molecular construct, therapeutic efficacy, and safety/challenges). However, I would recommend Neelapu 2019 in Hematological Oncology as an article focused more on CAR T-cell therapy adverse events/toxicities which includes quantitative data on toxicities.