Background/Purpose: CD19-targeted chimeric antigen receptor (CAR) T cell therapy is FDA-approved to treat lymphoma. A recent prospective case series of CD19 CAR T cell therapy suggested impressive efficacy for refractory autoimmune diseases; however, it had limited follow-up, small sample size, and no comparator group. Therefore, we identified patients with and without pre-existing autoimmune disease within a cohort of patients receiving CAR T cell therapy for lymphoma to investigate safety, cancer progression, and autoimmune disease activity.

Methods: We analyzed all patients receiving CD19 CAR T cell therapy for lymphoma through clinical care at a large cancer center and tertiary healthcare system (2017-2023). We identified patients in this cohort with pre-existing autoimmune disease through medical record review and collected data on disease type, immunomodulator use, and flares. We collected baseline characteristics at CAR T cell infusion and post-infusion outcomes including cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), lymphoma progression, and total mortality. We investigated whether pre-existing autoimmune disease was associated with presence and/or severity of CRS and ICANS using multivariable logistic regression. We analyzed whether pre-existing autoimmune disease was associated with lymphoma progression-free survival and total mortality using Cox regression. Finally, among only those with pre-existing autoimmune disease, we compared immunosuppression use and flare the year before vs. after CAR T cell therapy using paired McNemar’s tests.

Results: Among 499 patients with lymphoma who received CD19 CAR T cell therapy, 47 patients had pre-existing autoimmune disease. The most common pre-existing autoimmune disease was psoriasis (n=10); n=12 had a systemic rheumatic disease (Table 1). CRS occurred in 78.7% of those with vs. 83.4% without pre-existing autoimmune disease (multivariable OR 0.72, 95%CI 0.34-1.53, Table 2). ICANS occurred in 55.3% of those with vs. 49.6% without pre-existing autoimmune disease (OR 1.23, 95%CI 0.66-2.28). There was no difference in the use of tocilizumab for CRS nor any difference in severe (grade 3+) ICANS. During median follow-up of 9.4 months, there were 208 progression events and 164 deaths. There were no associations of pre-existing autoimmune disease with lymphoma progression (HR 1.15, 95%CI 0.77-1.72, Figure 1) or total mortality (HR 1.50, 95%CI 0.95-2.35). Among patients with autoimmune disease, there was less immunomodulator use (25% vs. 13%, p=0.008) and flare (15% vs. 5%, p=0.058) in the year after CAR T cell therapy compared to the year before.

Conclusion: In this first comparative CAR T cell therapy study, patients with pre-existing autoimmune disease had similar safety and lymphoma outcomes compared to those without. Treatment and flares of autoimmune disease were improved. These findings are reassuring for safety of CD19 CAR T cell therapy for lymphoma among patients with autoimmune diseases and inform ongoing prospective studies of CAR T cell therapy to treat autoimmune diseases.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/safety-cancer-progression-and-autoimmune-disease-activity-in-patients-with-pre-existing-autoimmune-disease-undergoing-cd19-car-t-cell-therapy-for-lymphoma-a-retrospective-comparative-cohort-study/