Influence of pre-existing autoimmune disease on outcomes in patients treated with CD-19 targeting CAR-t cell therapy for lymphoma: A retrospective propensity score matched study utilizing TriNetX.

Abstract

7033 Background: There is a lack of studies in the literature about the impact of baseline autoimmune diseases (AD) on outcomes in patients with lymphoma treated with CD-19 targeting-chimeric antigen receptor T-cell (CAR-T) therapy. This retrospective propensity score matched study aims to provide real-world evidence to understand the impact of pre-existing AD on outcomes in this population. Methods: This multicenter retrospective study included 504 patients with pre-existing AD diagnoses prior to receiving treatment with CD-19 targeting CAR-T therapy for lymphoma and 504, 1:1 propensity-score matched controls, without pre-existing AD, in the TriNetX Network. The outcomes analyzed were 5-year mortality, development of cytokine release syndrome (CRS), development of immune effector cell-associated neurotoxicity syndrome (ICANS), all cause hospitalization, ICU level care, risk of infection, and steroid use. Kaplan-Meier analysis, hazard ratios (HR), risk ratios (RR), and 95% confidence intervals (CI) were used to assess the primary outcomes. Results: Patients with pre-existing AD diagnosis were not at a statistically significant increased risk of mortality when compared to non-AD patients (HR = 1.10 [95% CI, 0.90-1.36]; P= 0.081). Both all-cause hospitalization (RR, 1.07 [95% CI, 1.03-1.10]) and ICU level of care (RR, 1.49 [95% CI, 1.19-1.84]) were higher in the pre-existing AD group when compared to non-AD patients. There was an increased risk for development of CRS in the AD group when compared to the non-AD group (RR, 1.17 [95% CI, 1.06-1.28]). There was no significant difference in the development of ICANs between the AD and non-AD group (RR, 1.10 [95% CI, 0.88-1.37]). There was an increased risk of infection amongst the AD group when compared to the non-AD group (RR, 1.48 [95% CI, 1.32-1.66]). Steroid use was higher in the pre-existing AD group (RR, 1.22 [95% CI, 1.09-1.38]). There was no statistically significant difference in rates of subsequent bone marrow transplant in patients with the pre-existing AD compared to the non-AD group (RR, 1.17 [95% CI, 0.93 -1.47]). Conclusions: CD19 CAR T- therapy has emerged as a promising therapeutic option for patients with AD, given its capacity to target and eliminate B-cells, which are vital in the pathogenesis of many AD. To our knowledge, this study represents the largest examination of the real-world impact of a baseline AD on clinical outcomes in patients undergoing CD19-targeted CAR T-cell therapy for lymphoma. Our findings indicate that pre-existing AD is associated with an increased risk of hospitalization, ICU level of care, CRS, and infections, without significantly affecting survival probability. Clinical trials are ongoing to evaluate the efficacy and safety of CAR T therapy in patients with AD.