Background: Chimeric antigen receptor T-cell (CAR-T) therapies and bispecific T-cell engagers (BiTEs) are transformative immunotherapies for relapsed or refractory lymphoid malignancies, now commonly used in second line and third line settings, respectively. While both provide meaningful clinical benefits, they differ considerably in their mode of administration, cost, and toxicity. As therapeutic options expand, real-world toxicity data are increasingly relevant to guide treatment selection based on safety, accessibility, and patient-specific factors. In this study, we compared the adverse event profiles of CAR-T and BiTE therapies using data from the FDA Adverse Event Reporting System (FAERS).

Methods: We conducted a retrospective pharmacovigilance analysis using the FAERS database from Q1 2021 to Q4 2024. Adverse event (AE) reports associated with FDA-approved CAR-T cell therapies and BiTEs were identified using drug name-based string matching. Key toxicities of interest included neutropenia, neurotoxicity, cardiotoxicity, acute kidney injury, hepatotoxicity, venous and arterial thrombotic events. Reports were aggregated at the patient level using unique identifiers. For each AE, proportional reporting ratios (PRRs), reporting odds ratios (RORs), 95% confidence intervals (CIs), and two-tailed p-values were calculated to assess disproportionality between CAR-T and BiTE-associated reports. A p-value <0.05 was considered statistically significant.

Results: A total of 155,821 AE reports involving BiTEs and 109,001 reports involving CAR-T cell therapies were identified in the FAERS database from 2021 to 2024.

Neutropeniawas reported in 20.2% of BiTE-associated reports and 11.6% of CAR-T-associated reports. BiTEs demonstrated a significantly higher disproportionality signal for neutropenia compared to CAR-T therapies (PRR=1.74, ROR=1.93, 95% CI [1.89, 1.98], p<0.001), with Glofitamab showing the highest reporting rate (42.2%) among BiTEs.

Conversely, neurotoxicity was more frequently reported with CAR-T therapies (36.1%) than BiTEs (5.2%). BiTEs had a significantly lower disproportionality signal (PRR=0.14, ROR=0.10, 95% CI [0.09, 0.10], p<0.001). Brexucabtagene autoleucel had the highest neurotoxicity rate (51.8%) among CAR-T agents.

Cardiotoxicity was also more frequently reported with CAR-T therapies (8.15%) than BiTEs (3.4%), with a significantly lower disproportionality signal for BiTEs (PRR=0.42, ROR=0.40, 95% CI [0.39, 0.41], p<0.001). Brexucabtagene autoleucel again had the highest cardiotoxicity rate (18.1%) among CAR-T agents.

Acute kidney injury was reported in 7.3% of CAR-T and 4.8% of BiTE-associated reports. BiTEs had a lower disproportionality signal (PRR=0.66, ROR=0.64, 95% CI [0.62, 0.66], p<0.001). Brexucabtagene autoleucel had the highest renal injury rate (15.4%) among CAR-T agents.

Similarly, hepatotoxicity was more frequent with CAR-T therapies (2.2% vs 1.0%), with BiTEs showing a significantly lower disproportionality signal (PRR=0.48, ROR=0.47, 95% CI [0.45, 0.51], p<0.001). Tisagenlecleucel had the highest hepatotoxicity rate (4.1%) among CAR-T agents.

Venous thrombosis was reported more often with CAR-T therapies (37.5%) than BiTEs (35.1%), corresponding to a lower disproportionality signal for BiTEs (PRR=0.93, ROR=0.90, 95% CI [0.89, 0.91], p<0.001). Axicabtagene ciloleucel had the highest venous thrombosis rate (42.6%) among CAR-T agents.

Arterial thrombosis was more frequent with CAR-T therapies (0.24% vs 0.09% in BiTEs), with BiTEs showing a significantly lower disproportionality signal (PRR=0.36, ROR=0.36, 95% CI [0.29, 0.44], p<0.001). Brexucabtagene autoleucel had the highest rate of arterial thrombosis (0.78%) among CAR-T agents.

Conclusion: This real-world analysis reinforces the well-characterized neurotoxicity associated with CAR-T therapies, while highlighting the higher rate of neutropenia with BiTEs. These distinct toxicity profiles emphasize the importance of individualized treatment selection, considering patient comorbidities, toxicity tolerance, logistical factors, and the clinical context, which includes the potential for better disease control with specific therapies.

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2025
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