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Real-World Dermatologic Adverse Events of CAR T-Cell Therapy: A Decade-Wide Disproportionality Analysis of the FDA Adverse Event Reporting System
1
Hull York Medical School, University of Hull, Hull HU6 7RX, UK
2
Haematology, Hull University Teaching Hospitals NHS Trust, Hull HU16 5JQ, UK
3
Translational Medical Sciences, School of Medicine, University of Nottingham, Nottingham NG7 2UH, UK
4
NIHR Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and the University of Nottingham, Nottingham NG7 2UH, UK
5
Sheffield Teaching Hospitals NHS Trust, Sheffield S5 7AU, UK
6
School of Medicine, Dentistry and Biomedical Sciences, Queen’s University Belfast, Belfast BT9 7BL, UK
7
Yale New Haven Hospital, New Haven, CT 06510, USA
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Cancers 2026, 18(13), 2128; https://doi.org/10.3390/cancers18132128
Submission received: 29 May 2026
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Revised: 23 June 2026
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Accepted: 30 June 2026
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Published: 30 June 2026
(This article belongs to the Section Cancer Therapy)
Simple Summary
CAR T-cell therapy is an important treatment for some blood cancers, but skin-related side effects after treatment are not well understood. We analysed more than 8.4 million reports from the FDA Adverse Event Reporting System to examine skin adverse-event reporting across seven approved CAR T-cell products. Overall, CAR T-cell therapy was not associated with increased reporting of skin adverse events compared with other reports in the database. Severe skin events were uncommon, but when reported, they often occurred early after treatment and overlapped with cytokine release syndrome, infection, low blood counts, bleeding-related features, or supportive-care medicines. One small vascular skin lesion associated with tisagenlecleucel was observed, but this became weaker after accounting for infection and cytopenia/bleeding-related reports. These findings should not be interpreted as showing that CAR T-cell therapy reduces the true clinical risk of skin toxicity, because spontaneous reporting databases measure reporting patterns rather than incidence. Clinically, a new severe rash or vascular skin changes after CAR T-cell therapy should prompt careful assessment for cytokine release syndrome, infection, cytopenias or bleeding, supportive care drug reactions, and true immune-mediated severe cutaneous adverse reactions.
Abstract
Background: Chimeric antigen receptor (CAR) T-cell therapy has transformed haematological-malignancy care, but its dermatologic safety profile remains incompletely characterised across products and indications. Methods: We analysed 8,431,841 deduplicated FDA Adverse Event Reporting System reports from 2016 Q3 to 2026 Q1. Seven approved CAR T-cell products were identified. The primary outcome was any dermatologic adverse event, defined using the MedDRA Skin and subcutaneous tissue disorders system organ class. Secondary outcomes included broad severe cutaneous adverse reactions, narrow Stevens-Johnson syndrome/toxic epidermal necrolysis, and 14 phenotype-specific categories. Multivariable models adjusted for demographics, polypharmacy, cancer, immune checkpoint inhibitor exposure, lymphodepleting chemotherapy and cytokine release syndrome. Additional sensitivity analyses evaluated HSCT/GVHD co-reporting proxies, infection and cytopenia/bleeding proxies, severe-event clinical characteristics, comparator robustness and multiplicity correction. Results: Dermatologic adverse events were identified in 996,654 reports, including 425 CAR-T-associated cases. CAR T-cell exposure was associated with reduced adjusted reporting odds for the primary outcome (adjusted odds ratio 0.13, 95% confidence interval 0.09–0.20) and broad severe cutaneous adverse reactions (0.35, 0.23–0.52). The primary SKIN_ANY reduced-reporting pattern was consistent across all-FAERS, haematological-malignancy and active haematology-oncology comparators. HSCT/GVHD proxy co-reporting was uncommon and did not materially alter estimates. Severe dermatologic reports frequently co-mentioned CRS and serious outcomes. The tisagenlecleucel vascular cutaneous signal was nominally significant but attenuated after excluding infection-attributable and cytopenia/bleeding-proxy reports. Conclusions: Within spontaneous reporting systems, CAR T-cell therapy showed reduced relative reporting of dermatologic adverse events across broad, phenotype-specific and product-level analyses. These results should be interpreted as differences in reporting behaviour, not as evidence of reduced true clinical incidence or lower patient-level risk. Early severe cutaneous reports frequently overlapped with cytokine release syndrome, while infection, cytopenia/bleeding proxies and supportive-care drugs were important alternative explanations for selected cutaneous signals.
