{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T09:47:34Z","timestamp":1782812854716,"version":"3.54.5"},"reference-count":60,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T00:00:00Z","timestamp":1782777600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>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\u2013Knapp\u2013Sidik\u2013Jonkman (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\u20131.89; 95% prediction interval (PI), 0.56\u20134.08), and non-Germinal center B-cell-like (GCB)\/ABC COO with worse adjusted progression-free survival (PFS) (HR 1.44; 95% CI, 1.04\u20132.00; 95% PI, 0.86\u20132.43). The complete-response analyses for TP53 alteration (OR 1.30; 95% CI, 0.01\u2013156.60) and COO (OR 1.27; 95% CI, 0.24\u20136.61) 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.<\/jats:p>","DOI":"10.3390\/genes17070752","type":"journal-article","created":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T08:26:15Z","timestamp":1782807975000},"page":"752","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Tumor Genomic Biomarkers as Prognostic Modifiers of Outcomes Following CD19 CAR T-Cell Therapy in Aggressive Large B-Cell Lymphoma: A Systematic Review and Exploratory Meta-Analysis"],"prefix":"10.3390","volume":"17","author":[{"given":"Jingke","family":"Yang","sequence":"first","affiliation":[{"name":"Parexel International, LLC., Raleigh, NC 27609, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-6065-9824","authenticated-orcid":false,"given":"Heather","family":"Hatcher","sequence":"additional","affiliation":[{"name":"Parexel International, LLC., Raleigh, NC 27609, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harshad","family":"Kulkarni","sequence":"additional","affiliation":[{"name":"Parexel International, LLC., Raleigh, NC 27609, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-6574-7559","authenticated-orcid":false,"given":"Chris A.","family":"Learn","sequence":"additional","affiliation":[{"name":"Parexel International, LLC., Raleigh, NC 27609, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1016\/S1470-2045(06)70664-7","article-title":"CHOP-like chemotherapy plus rituximab versus CHOP-like chemotherapy alone in young patients with good-prognosis diffuse large-B-cell lymphoma: A randomised controlled trial by the MabThera International Trial (MInT) Group","volume":"7","author":"Pfreundschuh","year":"2006","journal-title":"Lancet Oncol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1182\/bloodadvances.2025017120","article-title":"Outcomes for CART as 2L vs 3L vs 4L or beyond in aggressive B-cell lymphoma: Real-world evidence from the ABC Consortium","volume":"10","author":"Wang","year":"2026","journal-title":"Blood Adv."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e3202","DOI":"10.1002\/hon.3202","article-title":"Diffuse large B-cell lymphoma","volume":"42","author":"Barraclough","year":"2024","journal-title":"Hematol. 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