Endocrine toxicities in Chimeric Antigen Receptor T-Cell Therapy: A
pharmacovigilance study from 2017 to 2023 Quarter 1
Abstract
Aim: Chimeric antigen receptor (CAR)-T cell therapy represents a
revolutionary immunotherapy and cutting-edge strategy for cancer
treatment. However, the pharmacological safety of this approach in the
endocrine system has yet to be sufficiently validated. This study aims
to explore the potential toxicity signals of CAR T-cell therapy in the
endocrine system and their clinical relevance. Methods: This study
utilized data from the FDA Adverse Event Reporting System (FAERS)
database, covering 2017 to the first quarter of 2023 (Q1). Signal
detection of adverse events was achieved through the information
component method combined with the reporting odds ratio method. Results:
A total of 34,216,716 records were available in the FAERS database, and
60,730 records were screened for CAR T-cell therapy as the primary or
secondary suspected agent, identifying 12 positive endocrine signals
(preferred term), which represent a rare occurrence in the existing
literature on CAR T-cell therapy. Hyperglycemia topped the list with 42
reported cases (ROR025=1.01), followed by hypercalcemia
(n=26,ROR025=1.45) and adrenal insufficiency (n=15,ROR025=0.66).
Exophthalmos-related reports for tisagenlecleucel therapy showed the
highest death rate among the positive signals detected (5/6, 83.3%).
Adverse event reports related to conditions with fatal outcomes, such as
adrenal insufficiency (7/15, 46.7%), and hypercalcemia (13/25, 52.0%),
demonstrate significant overlap with cytokine release syndrome (CRS).
Conclusions: It is crucial for healthcare professionals to closely
monitor the potential adverse events related to the endocrine system
that may arise from CAR T-cell therapy. These events necessitate
thorough observation after treatment administration and the creation of
targeted prevention and treatment strategies