tisagenlecleucel 治疗复发/难治性弥漫大 B 细胞淋巴瘤的澳大利亚真实世界经验——CAR-T 治疗前优化的重要性

We report a single-center real-world analysis of patients with r/r DLBCL treated with tisagenlecleucel.

As of December 31, 2024, 63 patients with r/r DLBCL had received tisagenlecleucel (median follow-up, 15 months). Cytokine release syndrome occurred in 89%; 95% were grades 1/2. Immune effector cell-associated neurotoxicity syndrome was reported in 17% (10/11 cases mild; one case grade 3). The overall response rate was 79%, with 60% complete response (CR). The median duration of response was 26.4 months. The median progression-free survival (PFS) was 14.6 months, and the overall survival (OS) was 15.4 months. Patients whose response at day 30 was CR had a 42% reduction in risk of progression compared with those who achieved partial response (PR). High lactate dehydrogenase (LDH) at infusion was associated with a higher risk of disease progression (hazard ratio [HR] 2.1) and death (HR 2.65) than normal LDH, with the risk for progression increased 3.3-fold in a multivariate model. Almost one-third of our patients who achieved CR/PR had normalized their LDH at the time of infusion from a previously elevated level, of whom 87% (13/15) had received bridging therapy. Lack of response to bridging was associated with an almost twofold increased risk of progression compared with the responsive patients (3.1 vs. 19.5 months; HR 1.9; 95% CI: 0.9-3.9, P = 0.08).

We demonstrated in this analysis that the safety and efficacy of tisagenlecleucel in patients with r/r DLBCL in an Australian real-world setting were better than in the pivotal JULIET clinical trial and other registry studies. We also confirmed the importance of achieving early CR and normalizing the LDH levels at CAR-T cell infusion to reduce the risk of disease progression. Our results suggest that bridging therapy played an important role in optimizing outcomes by managing pre-CAR-T disease control.