Background:

Chimeric antigen receptor T-cell (CAR-T) therapy is an established management of relapsed and refractory lymphomas. However, its use in patients with pre-existing autoimmune diseases (AD) remains unclear due to concerns about increased immune-related toxicities and altered treatment efficacy. Interestingly, CAR-T therapy has also been explored as a potential option for managing severe, treatment-resistant autoimmune conditions. Despite this evolving interest, real-world data on the safety and outcomes of CAR-T therapy in lymphoma patients with coexisting autoimmune diseases remain limited. This study aims to evaluate and compare treatment outcomes, including efficacy and toxicity, of CAR-T therapy in lymphoma patients with and without pre-existing autoimmune diseases.

Methods:

We conducted a retrospective cohort study using the TriNetX platform, including adult patients (≥18 years) who underwent CAR T-cell therapy. Patients were stratified based on the presence or absence of pre-existing autoimmune disease (AD) before CAR T-cell therapy. Propensity score matching was performed to balance baseline characteristics, including demographics, lymphoma subtype, and use of immunosuppressive therapies such as corticosteroids, mycophenolate, and rituximab. The primary outcomes assessed were 5-year all-cause mortality, the incidence of cytokine release syndrome (CRS), and immune effector cell-associated neurotoxicity syndrome (ICANS). Secondary outcomes included intensive care unit (ICU) admission, all-cause hospitalization, seizure, cerebral infarct, and unspecified encephalopathy. All outcomes, except all-cause mortality, were assessed 90 days after CAR T-cell therapy. Encephalopathy was defined as a post-treatment diagnosis of encephalopathy without subclassification into metabolic, toxic, or other specific etiologies. Kaplan-Meier survival analysis, hazard ratios (HR), risk ratios (RR), and 95% confidence intervals (CI) were used to evaluate outcomes.

Results:

Baseline characteristics were well balanced following propensity score matching. A total of 629 patients were included in each group, with a mean follow-up duration of 157.5 days in the AD group and 159.0 days in the non-AD group. The mean age at index was 61.7 ± 13.2 years in the AD group and 61.6 ± 13.7 years in the non-AD group. Males comprised 52.95% of the AD group and 52.80% of the non-AD group, while females accounted for 45.81% and 46.27%, respectively. The majority of patients were White (77.02% in the AD group and 79.66% in the non-AD group), followed by African American patients (11.34% vs. 10.40%) and Asian patients (1.71% vs. 1.55%). Patients with AD did not have a statistically significant reduction in 5-year all-cause mortality compared to those without AD (HR 0.927; 95% CI: 0.751–1.143; p = 0.7509). The rates of all-cause hospitalization (RR 1.091; 95% CI: 0.923–1.29; p = 0.3237) and ICU admission (RR 1.16; 95% CI: 0.848–1.587; p = 0.3521) were higher in the AD group, although these differences were not statistically significant. Similarly, there were no significant differences in the incidence of ICANS (RR 0.998; 95% CI: 0.797–1.251; p = 0.9893), CRS (RR 1.112; 95% CI: 0.975–1.287; p = 0.1114), cerebral infarct (RR 1.667; 95% CI: 0.887–3.131; p = 0.1081), and seizures (RR 1.161; 95% CI: 0.826–1.63; p = 0.3894) between the two groups. However, patients with AD had a significantly higher risk of developing unspecified encephalopathy (RR 1.321; 95% CI: 1.005–1.734; p = 0.0446) following CAR-T therapy.

Conclusion:

This study demonstrates that lymphoma patients with pre-existing autoimmune disease can safely undergo CAR-T therapy with no increased risk of mortality or major treatment-related adverse events such as CRS, ICANS, cerebral infarct, or seizure. However, patients with pre-existing AD had a significantly increased risk of developing encephalopathy after CAR-T therapy. These findings suggest that CAR-T therapy remains a viable treatment option for patients with autoimmune disease, but increased neurologic monitoring may be required in this population.

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2025
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