Statin therapy with CD19-directed CAR-T therapy improves outcomes in relapsed or refractory large B-cell lymphoma

Statin exposure during treatment with CD19-directed CAR T for r/r LBCL is associated with improved responses and survival. Lipophilic statins have better outcomes and response rates than hydrophilic statins. Chimeric antigen receptor T-cell (CAR T) therapy has improved outcomes for patients with relapsed/refractory (r/r) large B-cell lymphoma (LBCL). However, up to 60% will eventually relapse. Hypercholesterolemia has been implicated in oncogenesis and T-cell exhaustion, and statin therapy has demonstrated proapoptotic and antitumor activity against lymphoma in preclinical models. This is a retrospective analysis comparing CD19-directed CAR T outcomes and response rates in statin-exposed and statin-non-exposed patients. Moreover, outcomes based on lipophilic vs. hydrophilic statin exposure were compared. Eighty-four patients with LBCL treated with FDA-approved CAR T therapies were included, with 32 (38.1%) being statin-exposed and 52 (61.9%) statin-non-exposed. Overall response rate (ORR) and complete response (CR) rate in the statin-exposed vs non-exposed groups following CAR T infusion were 81.3% vs. 65.3% (p=0.041), and 71.9% vs. 46.9% (p=0.027), respectively. Median progression-free survival (PFS) and overall survival (OS) for statin-exposed and non-exposed groups were not reached (NR) vs. 16.7 months [95% CI 4.6, 28.9] (p=0.026), and NR vs. 17.8 months [95% CI 10.3, 25.3] (p=0.032), respectively. Furthermore, lipophilic statins had a lower likelihood of progressive disease (p<0.001), improved OS (p=0.020), and lower lymphoma-related mortality (p=0.032) compared to hydrophilic statins. These findings suggest that statin exposure, particularly to lipophilic statins, enhances the efficacy of CD19-directed CAR T. A prospective trial is planned.