Baseline Tumor Transcriptional Features and Event-Free Survival After Anti-CD19 CAR T-Cell Therapy with Axicabtagene Ciloleucel in Large B-Cell Lymphoma: An Exploratory Reanalysis of the Randomized ZUMA-7 Trial
In brief
Eight tumor transcripts tracked with event-free survival after CAR T in lymphoma
In an exploratory reanalysis of 134 patients treated with axicabtagene ciloleucel, eight of 25 prioritized tumor transcripts were associated with event-free survival, and higher B-cell gene expression generally tracked with longer survival without an event. The findings do not establish that these markers predict who benefits from CAR T; independent validation is needed.
- Journal
- Medical sciences (Basel, Switzerland) (Q1)
- Published
- 13 October 2026
- Study design
- Randomized controlled trial
- Evidence level
- Level 1, High (CEBM 1b)
- Authors
- Jean Silva de Souza Resende, Igor Samesima Giner, Maria Gabriela Custodio de Figueiredo, Mariana Martins Paraízo, Enzo Lalli, Mauro Antônio Alves Castro, et al.
- PMID
- 42930590
- DOI
- 10.3390/medsci14060671
Why clinicians should know about it
- Picked for Hematology (top studies of the week, 1 November 2026): Exploratory biomarkers of event-free survival after LBCL CAR-T
Abstract
Background/Objectives: Anti-CD19 chimeric antigen receptor (CAR) T-cell therapy with axicabtagene ciloleucel (axi-cel) improves outcomes in relapsed/refractory large B-cell lymphoma (LBCL), but many patients relapse despite retained CD19 expression. We explored baseline tumor transcriptional features associated with event-free survival (EFS) after axi-cel. Methods: We reanalyzed baseline NanoString IO 360 profiles from the randomized ZUMA-7 trial (axi-cel, n = 134; standard of care [SOC], n = 122) using differential expression, gene set enrichment, MCP-counter deconvolution, Kaplan-Meier and Cox models adjusted for tumor burden and cell of origin, and gene-by-treatment interaction models. Results: T-cell exhaustion and HLA transcripts were not associated with response in either arm, and no transcript passed FDR correction in differential expression. In the axi-cel arm, 13 of 14 modeled transcripts remained associated with EFS after adjustment; eight (MS4A1, CD19, TNFRSF17, HLA-DOB, CD45RA, DUSP5, KLRD1 and WNT11) were FDR-supported at every survival-analysis stage within the 25 prioritized candidates, but not panel-wide. Consistent with the primary ZUMA-7 report, higher B-cell transcript expression was associated with longer EFS. Interaction testing gave borderline support for a differential association between arms only for KLRD1 and DUSP5 (FDR = 0.049), robust to arm-stratified models; other candidates showed no or only nominal specificity. Apart from the B-lineage score (FDR = 0.029), no estimated immune or stromal population was associated with response. Conclusions: Baseline B-cell transcriptional programs and a small set of gene-level candidates are associated with EFS after axi-cel in ZUMA-7. These exploratory findings do not establish predictive value and require independent validation.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.