Anbalcabtagene autoleucel 与 Tisagenlecleucel 在复发/难治性弥漫大 B 细胞淋巴瘤患者中的比较有效性

Anbalcabtagene autoleucel (anbal-cel) is a second-generation CD19-targeted chimeric antigen receptor T-cell therapy reducing T-cell exhaustion through programmed death-1 and T cell immunoreceptor with Ig and ITIM domains downregulation. We compared efficacy of anbal-cel with tisagenlecleucel (tisa-cel) in relapsed/refractory diffuse large B-cell lymphoma using external control arm study design.

We performed a matching-adjusted indirect comparison (MAIC) using individual patient data from CRC01-01 (NCT#04836507) and aggregate data from JULIET trial (NCT#02445248). Primary outcomes were overall survival (OS) and progression-free survival (PFS), with corresponding hazard ratio (HR) and 95% confidence interval (CI) assessed using weighted Cox proportional hazard model. Secondary outcomes were objective response rate (ORR) and complete response rate (CRR), with corresponding odds ratio (OR) and 95% CI assessed using weighted logistic regression model.

We included 79 patients in CRC01-01 and 115 in JULIET trial. In na ve comparison, median OS was not reached (95% CI, 13.1 to not estimable) for anbal-cel versus 11.1 months (95% CI, 6.6 to 23.9) for tisa-cel, corresponding to HR of 0.54 (95% CI, 0.34 to 0.87). Median PFS was 5.5 months (95% CI, 4.2 to 16.2) versus 2.9 months (95% CI, 2.3 to 5.2) with HR of 0.73 (95% CI, 0.50 to 1.08). ORR was 73.4% versus 53.0% with OR of 2.45 (95% CI, 1.32 to 4.54), and CRR was 64.6% versus 39.1% with OR of 2.83 (95% CI, 1.56 to 5.13). After applying MAIC to balance prognostic factors between the groups, adjusted HRs or ORs were 0.47 (95% CI, 0.23 to 0.95) for OS, 0.59 (95% CI, 0.36 to 0.96) for PFS, 2.60 (95% CI, 1.04 to 6.52) for ORR, and 3.00 (95% CI, 1.30 to 6.92) for CRR.

Anbal-cel showed superior effectiveness over tisa-cel, with higher response rates and improved survival outcomes, even after accounting for imbalances in prognostic factors at trial enrollment.