Statins May Improve Outcomes and Toxicities in Patients Undergoing CD19-Specific CAR T-Cell Therapy for Aggressive B-Cell Lymphomas

Introduction: Statins are both immunomodulatory and anti-inflammatory, and in-vivo studies have demonstrated pro-apoptotic effects in lymphoma cell lines. Moreover, they reduce T-cell exhaustion, which often limits anti-tumor activity and impacts the tumor microenvironment. While statin exposure has been associated with improved outcomes in patients receiving immune check-point inhibitors for solid tumor malignancies, it has not been evaluated in patients undergoing chimeric antigen receptor T-cell (CAR-T) therapy. Herein, we present an analysis of patient outcomes stratified by statin exposure in patients receiving CAR-T therapy targeting CD19 for aggressive B-cell lymphoma.

Methods: Patients diagnosed with aggressive B-cell lymphomas (high grade B-cell lymphoma or diffuse large B-cell lymphoma) who received CD19-CAR-T cells from January 2018 to May 2024 were included. Data was stratified based on statin vs non-statin exposure from time of cell collection to 12 -weeks after CAR-T cell infusion. Demographics, therapy data, treatment toxicities, rescue medications, standard lab parameters, and outcomes data were collected. Median overall survival (OS) and progression free survival (PFS) with 95% confidence interval (CI) were analyzed using Kaplan Meier methodology, and log-rank tests compared survival distributions. P<0.05 was considered statistically significant.

Results: There were 84 patients included, with a median age of 65 (24-78) years. Of these, 34 (40.5%) were females. A total of 32 (38.1%) patients had statin exposure and 52 (61.9%) had no statin exposure. The median ages of statin and non-statin cohorts were 71 (49-78) and 63 (24-77), respectively. Axicabtagene ciloleucel was used in 23 (71.8%) in statin and 42 (80.7%) in non-statin arm. Median prior lines of therapy were 2 (1-4) in both cohorts. Most patients received moderate (59.4%) and high intensity (34.4%) statins.

At last follow-up, 10 (31.2%) patients in the statin group and 22 (42.3%) in non-statin group had progressed, and 7 (21.9%) and 22 (42.3%) patients died, respectively. In the statin and non-statin arms, median PFS was not reached (NR) and 16.7 months (95% CI 4.6, 28.9) (p=0.026), respectively, and median OS was NR vs 17.8 months (95% CI 10.3, 25.3) (p=0.032), respectively.

Cytokine release syndrome (CRS) and immune effector cell neurotoxicity syndrome (ICANS) of any grade were reported in 75.0% and 80.8% (p=0.537) and 21.9% and 34.6% (p=0.220) in the statin and non-statin cohorts, respectively. Median grade CRS was 1 (1-2) and ICANS was 1 (1-2) in both cohorts; utilization of tocilizumab was 43.8% vs 63.5% (p=0.079) and dexamethasone was 40.6% vs 53.8% (p=0.21) in statin and non-statin cohorts, respectively. Inflammatory markers, including ferritin (p=0.256) and CRP (p=0.655), did not significantly differ.

Conclusion: Patients with aggressive B-cell lymphomas and statin exposure along with CD19-CAR-T had a significant improvement in PFS and OS, similar rate of toxicities, and a trend toward lower utilization of tocilizumab. Statin use may enhance efficacy and mitigate toxicities, and its role should be assessed in prospective trials.