Early lymphocyte collection for anti-CD19 CART production improves T-cell fitness in patients with relapsed/refractory diffuse large B-cell lymphoma

Abstract

Background: Chimeric antigen receptor (CAR) T cells targeted to the CD19 B-cell antigen form an approved treatment for patients with relapsed/refractory diffuse large B-cell lymphoma (r/r DLBCL). However, since this therapy is administered after multiple lines of treatment and exposure to lymphotoxic agents, there is an urgent need to optimize this modality of treatment. Methods: To circumvent the difficulties of harvesting adequate and optimal T cells from DLBCL patients and improve CART therapy, we suggest an earlier lymphopheresis (i.e. at first relapse, before salvage treatment). We conducted a prospective study and evaluated the potential benefit of an earlier lymphopheresis (early group, n = 22) on the clinical outcome of CD19-CART infused DLBCL patients, in comparison with standard lymphopheresis (i.e. at second relapse and beyond; standard group, n = 23). Results: An increased percentage of naïve T cells and increased in vitro T-cell functionality were observed in the early group. Additionally, these cells exhibit a lower exhaustion profile than T cells collected in the standard group. Conclusion: While improved T-cell phenotype and function in the lymphopheresis product did not translate into significantly improved clinical outcomes, a trend towards better overall survival (OS) and progression-free survival (PFS) was observed. Early lymphopheresis maximizes the potential of salvage therapies, without compromising CAR T-cell quality.