Long-Term Efficacy and Safety of CD19-Specific CAR-T Cells Armed with IL-7 and CCL19 in Patients with Relapsed or Refractory Large B-Cell Lymphoma: A Multi-Center Prospective Study

To further improve expansion, infiltration, persistence, and especially outcome, adjusting the Chimeric antigen receptor (CAR) structure to enhance antitumor efficiency is an important strategy. In this pattern, fourth-generation CAR-T, also named “armored CAR-T” or T cells redirected for universal cytokine killing (TRUCK), with the ability of expressing cytokines or chemokines, has been thoroughly evaluated in preclinical studies and clinical trials across various malignancies.

In our previous study, we developed a CD19-specific fourth-generation CAR-T expressing interleukin (IL)-7 and chemokine (C-C motif) ligand 19 (CCL19), named 7×19 CAR-T. In this long-term follow-up study of up to 5 years (NCT04833504), the 39 patients in the interim report were followed up for extended time.

Among these patients enrolled, the median age was 55 years (range, 29-73). Most of the patients (66.7%) had stage III or IV disease, 41% had an ECOG performance status score of 2 or 3, 64.1% had extranodal organ involvement, 51.3% had received at least three lines of previous therapies, 46.2% had received more than 10 times of prior treatment regimen, 51.3% had refractory disease, 7.7% experienced autologous stem cell transplantation (ASCT) and 46.2% had bulky disease defined as the presence of any mass with a single diameter over 7cm.

During a median follow-up of 63 months by reverse Kaplan-Meier method, 15 patients (38.5%) continued to survive at data cutoff. The median OS was 31 months, with an estimated 5-year OS of 43.6% (95% CI: 27.9 to 58.3%) among all patients and 64.6% among those achieving a CR. After excluding deaths unrelated to disease progression, the estimated disease-specific survival at 5 years reach 48.7% (95% CI: 32.4% to 63.2%). The median PFS was 13 months, with an estimated 5-year PFS of 30.8% (95% CI: 17.3% to 45.4%).

there was no significant difference between patients with or without bulky disease considering OS or PFS, which indicates that this armored CAR-T can to some extent overcome the adverse effect of bulky disease.

In summary, this updated 5-year analysis demonstrated the continued benefit of 7×19 CAR-T for in patients with Rel/Ref LBCL with satisfactory safety signals. The development of this study has laid a solid foundation for future frontline use or combined clinical research.