Real World Outcomes of Patients with Aggressive Lymphoma and Autoimmune Disease Treated with CART

TL;DR

This study shows that CAR-T therapy is safe and effective for aggressive lymphoma patients with autoimmune diseases, similar to those without.

Contribution

Provides real-world evidence of CAR-T efficacy and safety in lymphoma patients with autoimmune diseases, previously excluded from trials.

Findings

CAR-T safety and efficacy were comparable between patients with and without autoimmune diseases.

Infection rates were higher in the autoimmune disease cohort, but other adverse events were similar.

Three-year survival and progression-free survival rates were slightly lower in autoimmune disease patients but not significantly different.

Abstract

Autoimmune diseases (AIDs) are associated with the development of B-cell non-Hodgkin lymphomas (B-NHLs). Autologous chimeric antigen receptor T-cell therapy (CART) is an effective therapy approved for the treatment of lymphoma; however, patients with AIDs were excluded from trials that led to CART approval. The goal of this retrospective study was to compare clinical outcomes for patients treated with CART for aggressive B-NHL with and without underlying AIDs. We found that the safety profile and efficacy of CART were comparable between these two cohorts. We also provide data on the impact of CART on AID control. This provides real-world information on the utility of CART as treatment for lymphoma in patients with AIDs, as well as insight into its possible use in the treatment of AIDs alone.

Background/Objectives: There is an association between autoimmune disease (AID) and non-Hodgkin lymphoma (NHL). Chimeric antigen receptor T-cell therapy (CART) is approved for the treatment of aggressive B-cell NHL (B-NHL) based on pivotal trials that excluded patients with active AID and/or on chronic immunosuppressive therapy (IST). Thus, the efficacy of CART in patients with AID warrants further investigation. Methods: We identified patients with and without AID from a cohort of 727 patients treated with CART for aggressive B-NHL across 12 institutions. Overall survival (OS) and progression-free survival (PFS) were estimated using Kaplan-Meier survival curves. AID vs. non-AID patients were compared using log-rank tests. Results: Among our patients with aggressive B-NHL, 47 (6.4%) had concurrent AID. Rates of cytokine release syndrome and neurotoxicity were not significantly different between patients with and without AID (p = 0.5), while infection rates were higher in the AID cohort. For AID vs. non-AID patients, complete response rates were similar between the groups (38% vs. 36.0%, p = 0.36). The rates of relapse/progression post-CART were not significantly different (p = 0.07). Three-year PFS rates were 49% and 32%, respectively (p = 0.18); 3-year OS rates were 57% and 44%, respectively (p = 0.25). Prior to CART, 32% of patients with AID were on IST; 6 (13%) patients with AID either remained on IST during CART or resumed IST post-CART, and 1 patient newly started IST following CART. Conclusions: In the real-world setting, despite inherent T-cell dysfunction expected in B-NHL patients with concurrent AID, the safety and efficacy of CART is comparable with durable responses.

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