肿瘤基因组生物标志物作为侵袭性大 B 细胞淋巴瘤 CD19 CAR-T 细胞治疗后结局的预后修饰因素：系统综述与探索性荟萃分析

Background/Objectives : Outcomes after CD19-directed chimeric antigen receptor (CAR) T-cell therapy for relapsed or refractory (R/R) aggressive large B-cell lymphoma (aLBCL) remain heterogeneous. Tumor genomic biomarkers, such as TP53 alteration, MYC/BCL2/BCL6 rearrangement-defined double-hit or triple-hit lymphoma (DHL/THL), cell of origin (COO), and complex karyotype, are established or candidate prognostic factors in conventionally treated lymphoma, but their relevance after CAR T-cell therapy is uncertain.

We conducted a systematic review with exploratory meta-analysis of biomarker-stratified outcomes after CD19 CAR T-cell therapy in aLBCL. Methods : We searched MEDLINE, Embase, and Web of Science/BIOSIS (April 2026), with targeted PubMed citation lookup during full-text retrieval (PROSPERO CRD420261350514). Eligible studies enrolled adults with R/R disease treated with protocol-eligible CD19 CAR T-cell therapy and reported prespecified tumor genomic biomarkers with stratified outcomes. Random-effects models, using restricted maximum-likelihood estimation with Hartung-Knapp-Sidik-Jonkman (HKSJ) adjustment, were fitted when at least three comparable, non-overlapping studies provided extractable data. Results : After duplicate removal, 182 records were screened, 37 were assessed for eligibility, and 26 studies were included in the qualitative synthesis; 10 contributed to 4 pooled analyses. DHL/THL-positive disease was associated with worse unadjusted overall survival (OS) (hazard ratio [HR] 1.

52; 95% confidence interval [CI], 1. 21-1. 89; 95% prediction interval (PI), 0. 56-4. 08), and non-Germinal center B-cell-like (GCB)/ABC COO with worse adjusted progression-free survival (PFS) (HR 1. 44; 95% CI, 1. 04-2. 00; 95% PI, 0. 86-2. 43). The complete-response analyses for TP53 alteration (OR 1. 30; 95% CI, 0. 01-156. 60) and COO (OR 1. 27; 95% CI, 0. 24-6. 61) were statistically uninformative. No study permitted evaluation of complex karyotypes.

Conclusions : Biomarker-stratified evidence after CD19 CAR T-cell therapy is sparse and inconsistently reported. DHL/THL status and non-GCB/activated B-cell-like (ABC) COO showed exploratory survival signals, whereas the TP53 and COO complete-response analyses were uninformative. These biomarkers remain hypothesis-generating rather than validated predictors of CAR T-cell outcome, and standardized, prospective biomarker-stratified reporting is needed.