大 B 细胞淋巴瘤中早期与晚期引入 CAR-T 细胞治疗的治疗失败模式

CD19-directed chimeric antigen receptor T-cell (CAR-T) therapy has recently been approved as second-line treatment for relapsed/refractory large B-cell lymphoma (LBCL).

This study compares patterns of disease relapse and progression across patients receiving CAR-T as second-line (early administration) versus third or subsequent lines (late administration).

We analyzed 354 patients treated with Axicabtagene ciloleucel (71%) and Lisocabtagene maraleucel (29%); 80 (23%) received early administration, and 274 (77%) late administration. One-year overall survival was higher in the early group (82% [95% CI 72-93] vs. 71% [95% CI 66-77], p = 0. 048).

However, the survival benefit was not sustained in multivariable Cox regression modeling and propensity score matching. One-year cumulative incidences of relapse were similar (37% [95% CI 24-50] vs. 43% [95% CI 37-49], p = 0. 2), as were 1-year progression-free survival probabilities (62% [95% CI 50-76] vs.

50% [95% CI 44-57], p = 0. 14). The early group exhibited a favorable toxicity profile, with lower rate of grade 2 cytokine release syndrome (26% vs. 39%, p = 0. 031) and reduced cumulative incidence of severe neutropenia (41% [95% CI 30-52] vs. 55% [95% CI 49-60], p = 0. 027).

Our results indicate favorable outcomes with CAR-T irrespective of treatment line. The equivalence in disease control suggests that CAR-T resistance mechanisms persist in LBCL failing first-line therapy.