Prolonging Life Without Progression in Large B-Cell Lymphoma: Real-World Insights

After treatment with tisagenlecleucel (tisa-cel), there may be a 2-year period for observation of disease progression in patients with large B-cell lymphoma (LBCL). In comparison, complete remissions may be sustained at one year in these patients after treatment with either axicabtagene ciloleucel (axi-cel) or lisocabtagene maraleucel (liso-cel) with low probability of relapse, according to real-world findings.

With the number of chimeric antigen receptor (CAR) T-cell therapies available for large B-cell lymphoma, response rates in this patient population have greatly improved, but relapse rates remain an area of concern for hematologic oncologists.

There is uncertainty about how inducing a complete response (CR) and maintaining said response correlates with long-term progression-free survival (PFS) and overall survival (OS). Because clinical trials have not compared the three available CAR T-cell therapies, there are also questions about which agent is more efficacious. Furthermore, research has yet to identify key prognostic factors that impact efficacy outcomes of CAR T-cell therapy in patients with LBCL.

A retrospective, multicenter analysis was conducted with 479 patients with LBCL. The patients were treated with tisa-cel, axi-cel, or liso-cel between April 2018 and June 2023. The patients were evaluated for the co-primary endpoints of PFS and OS. The PFS curves were also used to evaluate CRs.

The median duration of follow-up was 18 months in the axi-cel group, 34 months in the tisa-cel group, and 12 months in the liso-cel group. The median PFS was 12 months in patients treated with axi-cel, 3.2 months in the tisa-cel group, and not reached in patients treated with liso-cel. A CR observed at day 28 appeared to continue through day 100. Notably, among the axi-cel– and liso-cel–treated patients, conversion from a partial response to a CR was observed more frequently than among patients with a CR who developed disease progression.

When the correlation between CR at day 28 and PFS was examined, results showed that in the 195 patients who had a CR at day 28, the PFS rate was 64% at one year and 53% at two years. By the 12-month landmark, PFS rates were 87% for patients in the axi-cel group, 100% for those in the liso-cel group, and 85% for those in the tisa-cel group; and remissions were maintained through 24 months. Overall, elevated lactate dehydrogenase (LDH) levels before lymphodepletion (P <.05), type of response to CAR T cells (P =.002), and CAR-T product (P =.025) significantly correlated with PFS.

Taken together, the real-world findings suggest that treatment with either axi-cel or liso-cel provides potential to sustain disease-free survival in patients with LBCL.

Reference

Gomez-Llobell M, Shouval R, Brown S, et al. When can we define disease-free status post-CAR-T therapy in LBCL? Findings from dynamic landmark analyses. Presented at 2025 Transplantation & Cellular Therapy Meetings of the ASTCT and CIBMTR; February 12-15, 2025; Honolulu, HI. Abstract 213.