Danny Luan, Susan DeWolf, Teng Fei, Sandeep Raj, Gunjan L Shah, Caleb A Lareau, Mohammad Alhomoud, Gilles Salles, Alfredo Rivas-Delgado, Kai Rejeski, Jae H Park, Efrat Luttwak, Alejandro Luna de Abia, Magdalena Corona, Evangelos Ntrivalas, Giulio Cassanello, Marina Gomez-Llobell, Allison Parascondola, Michael Scordo, Katharine C Hsu, M Lia Palomba, Miguel-Angel Perales, Roni Shouval
{"title":"Dynamics of Immune Reconstitution and Impact on Outcomes across CAR-T Cell Products in Large B-cell Lymphoma.","authors":"Danny Luan, Susan DeWolf, Teng Fei, Sandeep Raj, Gunjan L Shah, Caleb A Lareau, Mohammad Alhomoud, Gilles Salles, Alfredo Rivas-Delgado, Kai Rejeski, Jae H Park, Efrat Luttwak, Alejandro Luna de Abia, Magdalena Corona, Evangelos Ntrivalas, Giulio Cassanello, Marina Gomez-Llobell, Allison Parascondola, Michael Scordo, Katharine C Hsu, M Lia Palomba, Miguel-Angel Perales, Roni Shouval","doi":"10.1158/2643-3230.BCD-24-0163","DOIUrl":null,"url":null,"abstract":"<p><strong>Abstract: </strong>Patients treated with chimeric antigen receptor T-cell (CAR-T) therapy are subject to profound immunosuppression. Dynamics of immune reconstitution (IR) and impacts of IR on outcomes following infusion across CAR-T products are not well understood. In this study, we profiled IR in 263 patients with relapsed/refractory large B-cell lymphoma receiving CAR-T therapy (axicabtagene ciloleucel 44.9%, lisocabtagene maraleucel 30.4%, and tisagenlecleucel 24.7%). Following infusion, patients remain persistently immunosuppressed, with 48.1% having CD4+ T-cell counts <200/µL and the median CD3-CD19+ B-cell counts remaining zero through 1 year after CAR-T therapy. IR differences exist by product, with the fastest CD4+ T-cell recovery seen for tisagenlecleucel, driven primarily by more rapid recovery of the CD4+CCR7−CD45RA− effector memory subset. NK cell, but not CD4+ T cell, recovery is significantly associated with favorable progression-free (HR, 0.65; 95% confidence interval, 0.48–0.88) and overall survival (HR, 0.64; 95% confidence interval, 0.44–0.92) and inversely correlated with inflammatory markers measured at the time of infusion.</p><p><strong>Significance: </strong>This study reveals differences in IR patterns after CAR-T therapy in patients with large B-cell lymphoma, with early NK cell recovery emerging as a key predictor of survival. These findings provide potential future avenues of research for improving patient outcomes and tailoring post-therapy management strategies to mitigate relapse risk.</p>","PeriodicalId":29944,"journal":{"name":"Blood Cancer Discovery","volume":" ","pages":"119-130"},"PeriodicalIF":11.5000,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11876948/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Blood Cancer Discovery","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1158/2643-3230.BCD-24-0163","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"HEMATOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Abstract: Patients treated with chimeric antigen receptor T-cell (CAR-T) therapy are subject to profound immunosuppression. Dynamics of immune reconstitution (IR) and impacts of IR on outcomes following infusion across CAR-T products are not well understood. In this study, we profiled IR in 263 patients with relapsed/refractory large B-cell lymphoma receiving CAR-T therapy (axicabtagene ciloleucel 44.9%, lisocabtagene maraleucel 30.4%, and tisagenlecleucel 24.7%). Following infusion, patients remain persistently immunosuppressed, with 48.1% having CD4+ T-cell counts <200/µL and the median CD3-CD19+ B-cell counts remaining zero through 1 year after CAR-T therapy. IR differences exist by product, with the fastest CD4+ T-cell recovery seen for tisagenlecleucel, driven primarily by more rapid recovery of the CD4+CCR7−CD45RA− effector memory subset. NK cell, but not CD4+ T cell, recovery is significantly associated with favorable progression-free (HR, 0.65; 95% confidence interval, 0.48–0.88) and overall survival (HR, 0.64; 95% confidence interval, 0.44–0.92) and inversely correlated with inflammatory markers measured at the time of infusion.
Significance: This study reveals differences in IR patterns after CAR-T therapy in patients with large B-cell lymphoma, with early NK cell recovery emerging as a key predictor of survival. These findings provide potential future avenues of research for improving patient outcomes and tailoring post-therapy management strategies to mitigate relapse risk.
期刊介绍：
The journal Blood Cancer Discovery publishes high-quality Research Articles and Briefs that focus on major advances in basic, translational, and clinical research of leukemia, lymphoma, myeloma, and associated diseases. The topics covered include molecular and cellular features of pathogenesis, therapy response and relapse, transcriptional circuits, stem cells, differentiation, microenvironment, metabolism, immunity, mutagenesis, and clonal evolution. These subjects are investigated in both animal disease models and high-dimensional clinical data landscapes.
The journal also welcomes submissions on new pharmacological, biological, and living cell therapies, as well as new diagnostic tools. They are interested in prognostic, diagnostic, and pharmacodynamic biomarkers, and computational and machine learning approaches to personalized medicine. The scope of submissions ranges from preclinical proof of concept to clinical trials and real-world evidence.
Blood Cancer Discovery serves as a forum for diverse ideas that shape future research directions in hematooncology. In addition to Research Articles and Briefs, the journal also publishes Reviews, Perspectives, and Commentaries on topics of broad interest in the field.
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