Chimeric antigen receptor T-cell immunotherapies adverse events reported to FAERS database: focus on cytopenias

Abstract

Chimeric antigen receptor (CAR) T-cell therapy presents a promising treatment for hematologic malignancies, displaying high efficacy but not being exempt from toxicity. In this observational study, we assessed adverse events (AEs) reported to the Food and Drug Adverse Event Reporting System (FAERS) including any of the six approved CAR T-cell therapies. A total of 5249 reports mentioning a CAR T-cell as a suspect product were retrieved from the FAERS database, containing a total of 24333 AEs, of which 3236 (13.3%) were cytopenias. The highest number of AEs mentioned by the report was observed for tisagenlecleucel (mean = 6.7), with the lowest for ciltacabtagene (mean = 1.3). Among all reports, hematopoietic leukopenia was the most frequently reported AEs (n = 1386, 5.7%), with hematopoietic erytropenia the least reported (n = 291, 1.2%). Tisagenlecleucel showed a high reporting odds ratio for hematopoietic erythropenia (27.28, 95%CI 14.04–53.00), leukopenia (4.04, 95%CI 3.52–4.64), and thrombocytopenia (4.01, 95%CI 3.19–5.03). Cytopenias represent one of the most frequently reported AEs in FAERS, a CAR T-cell therapy is indicated, with haematopoetic leukopenia being the most common. When comparing different CAR-T cell therapies, the cytopenias’ reporting odds ratio was particularly high for tisagenlecleucel, especially in relation to hematopoietic erythropenia.

Keywords:

• Receptors
• chimeric antigen
• drug-related side effects and adverse reactions
• adverse drug reaction reporting systems
• pharmacovigilance
• hematologic diseases

Ethics statement

The FDA Adverse Event Reporting System (FAERS) database is publicly available and informed consent and local IRB approval are required to conduct studies using this database.

Disclosure statement

The authors report that there are no competing interests to declare.

Data availability statement

The source data for this study are publicly available. FAERS data is publicly available at: https://www.fda.gov/drugs/questions-and-answers-fdas-adverse-event-reporting-system- HYPERLINK "https://www.fda.gov/drugs/questions-and-answers-fdas-adverse-event-reporting-system-faers/fda-adverse-event-reporting-system-faers-public-dashboard"faers/fda-adverse-event-reporting-system-faers-public-dashboard. Analytical datasets are available from the corresponding author on reasonable request.

Correction Statement

This article has been corrected with minor changes. These changes do not impact the academic content of the article.

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.