完全缓解对复发/难治性大 B 细胞淋巴瘤患者长期生存的影响：国际血液与骨髓移植研究中心前瞻性研究及系统综述/荟萃分析

In oncology, overall survival (OS) is the benchmark endpoint for assessing therapy effectiveness, but requires large patient cohorts and extended follow-up to attain meaningful data. The identification of reliable surrogate markers for OS may enable earlier treatment decisions and streamline clinical trial design, potentially reducing costs and accelerating access to new therapies.

The objective of this study was to evaluate whether complete response (CR) could serve as an early surrogate for OS in patients with relapsed or refractory large B-cell lymphoma (r/r LBCL).

This study used two data sources: a systematic literature review (SLR) with meta-analyses and patient-level real-world data from the Center for International Blood and Marrow Transplant Research (CIBMTR) registry evaluating the chimeric antigen receptor (CAR) T-cell therapy axicabtagene ciloleucel (axi-cel). Systematic searches of PubMed and EMBASE were conducted to identify clinical trials and real-world cohort studies published between January 2000 and July 2024 that reported CR rates and 1- and 2-yr OS rates in patients who received systemic treatment for r/r LBCL. Meta-analyses were stratified by treatment type, study type, median lines of prior therapy, response criteria, and high-risk status. The CIBMTR study included adult patients with r/r LBCL treated with axi-cel between October 2017 and August 2020 and collected data on CR rate, time to CR (TtCR), and OS. Multivariable analyses adjusted for key prognostic factors were conducted to identify baseline patient characteristics associated with TtCR and OS at Day 100 and Month 6 after axi-cel infusion and to determine the association between OS and CR at Day 100 and Month 6. In the SLR/meta-analysis, a total of 82 original articles were identified through PubMed and EMBASE searches and secondary references.

CR rates across treatment modalities were strongly predictive of achieving OS at 1 and 2 yr after treatment in patients with r/r LBCL who were in high-risk cohorts (R 2 : 1 yr, 0. 86; 2 yr, 0. 89) or cohorts with a median of 3 prior therapy lines (R 2 : 1 yr, 0. 89; 2 yr, 0. 96). Of the 1251 patients included in the CIBMTR analysis, 60% (95% confidence interval [CI], 57% to 63%) achieved CR with axi-cel; 90% of initial CRs occurred within 6 mo of axi-cel infusion (median follow-up, 36. 9 mo).

Earlier achievement of CR was associated with older age, better Eastern Cooperative Oncology Group performance status, lower tumor burden, and prior autologous hematopoietic cell transplantation. In multivariable analyses, OS was significantly higher in patients who were in CR at Day 100 (hazard ratio [HR] 0. 33; 95% CI, 0. 27 to 0.

40) or Month 6 (HR 0. 24; 95% CI, 0. 20 to 0. 30) after axi-cel infusion compared with those who did not achieve CR by those time points, respectively. These results suggest that CR at Day 100 or Month 6 are viable surrogate endpoints for OS in patients who receive CAR T-cell therapies, supporting their inclusion as endpoints in clinical trial design.