Researchers say they have identified 28 signs and symptoms that can facilitate early recognition of toxicity associated with chimeric antigen receptor (CAR) T-cell therapy. The findings were published in JCO Oncology Practice.
Researchers performed a review of phase 2/3 trials of CAR T-cell products approved for use in the United States and identified common and severe adverse events that could be translated into patient- and caregiver-reported outcomes.
Nine relevant studies were identified, and 457 adverse events were reviewed by 11 CAR T-cell-dedicated hematologists from the Dutch CAR T-cell tumor board.
After several rounds of review, the final list included 28 signs and symptoms, more than half of which are neurological.
“This might be explained by the fact that the clinical spectrum of ICANS [immune effector cell-associated neurotoxicity syndrome] is very heterogeneous,” the researchers wrote. “In addition, most neurological symptoms are considered possible red flags since ICANS can start with subtle changes in mental status, such as difficulty in writing or naming objects, but can rapidly progress and become life-threatening, requiring prompt management.”
Among the signs and symptoms on the list are 5 that can be monitored using devices — hypertension, hypotension, tachycardia, hypoxemia, and fever.
Another 2 items on the list — encephalopathy and level of consciousness — can be evaluated using the immune-effector cell-associated encephalopathy (ICE) test and the alert, responsive to voice, responsive to pain, unresponsive level of consciousness (AVPU) assessment.
The remaining 21 items on the list can be reported by the patient or the caregiver and include symptoms such as dizziness, cough, diarrhea, vomiting, and shortness of breath.
The researchers noted that both pain and fatigue were excluded from the list, “illustrating the focus of this study being on selecting specific signs and symptoms considered as possible acute CAR T-cell–related toxicity that warrant immediate action.”
One limitation of the study is the inclusion of only Dutch experts. International validation of these signs and symptoms could be of value, the researchers wrote.
“If this framework incorporated in an eHealth tool is proven to have adequate usability and feasibility, this tool could be used in studies investigating strategies to reduce hospital visits in the first month after CAR T-cell infusion and/or enable early discharge or even complete ambulatory treatment,” the researchers concluded.
Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
Spanjaart AM, Pennings ERA, Kos M, et al. Development of a core set of patient- and caregiver-reported signs and symptoms to facilitate early recognition of acute chimeric antigen receptor T-cell therapy toxicities. JCO Oncol Pract. Published online December 12, 2022. doi:10.1200/OP.22.00501