Evaluation of in vivo CAR transgene levels in tisagenlecleucel-treated patients with relapsed/refractory B-ALL and DLBCL

Tisagenlecleucel is a CD19-directed autologous chimeric antigen receptor (CAR) T-cell therapy. Quantitative polymerase chain reaction assays are highly sensitive in defining in vivo kinetics by measuring CAR transgene in peripheral blood. This study aimed to identify clinically meaningful CAR T-cell blood levels that correlated with response/relapse. In pediatric/young adult patients with relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL), maximum CAR T-cell blood levels were higher in patients with ongoing complete remission and in patients with CD19- relapse relative to those with CD19+ relapse. In adult patients with R/R diffuse large B-cell lymphoma (DLBCL), no apparent association between in vivo kinetics and response was noted, with a wide range of transgene levels at relapse. In B-ALL, patients with B-cell aplasia sustained >6 months had higher CAR T-cell expansion relative to those with early B-cell recovery (BCR) (<6 months after infusion); however, a definitive cutoff for BCR-associated expansion level could not be identified. In most patients with B-ALL, BCR >6 months maintained favorable responses. However, early BCR could not be confirmed as a potential indicator of relapse due to high censoring from transplant, following presumed risk of relapse. However, allografting in these patients may potentially mitigate the poor prognosis related to early BCR. In DLBCL, BCR was not associated with relapse. These findings suggest that blood CAR transgene levels may be associated with long-term responses; however, they lack robust predictive potential for relapses. As reported earlier, next-generation sequencing for minimal residual disease appears to be a reliable biomarker predictive of relapse for B-ALL.

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Publication Details

Journal
Blood Advances
Published
2025-06-24
DOI
https://doi.org/10.1182/bloodadvances.2024014995
Primary Topic
CAR-T cell therapy research
Type
article
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0.00

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article

Evaluation of in vivo CAR transgene levels in tisagenlecleucel-treated patients with relapsed/refractory B-ALL and DLBCL

Michael A. Pulsipher, Edmund K. Waller, Gary Douglas Myers, Susana Rives et al.
Blood Advances
CAR-T cell therapy research
article

Evaluation of in vivo CAR transgene levels in tisagenlecleucel-treated patients with relapsed/refractory B-ALL and DLBCL

Michael A. Pulsipher, Edmund K. Waller, Gary Douglas Myers, Susana Rives, Abhijit Chakraborty, Constantine Si Lun Tam, Ulrich Jäger, Joseph P. McGuirk, Heather E. Stefanski, Aisha Masood, Peter Borchmann, Stephan A. Grupp, Stephen J. Schuster, Gregory A. Yanik, Michael R. Bishop, André Baruchel, Rakesh Awasthi, Edward Waldron
article en

Abstract

Tisagenlecleucel is a CD19-directed autologous chimeric antigen receptor (CAR) T-cell therapy. Quantitative polymerase chain reaction assays are highly sensitive in defining in vivo kinetics by measuring CAR transgene in peripheral blood. This study aimed to identify clinically meaningful CAR T-cell blood levels that correlated with response/relapse. In pediatric/young adult patients with relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL), maximum CAR T-cell blood levels were higher in patients with ongoing complete remission and in patients with CD19- relapse relative to those with CD19+ relapse. In adult patients with R/R diffuse large B-cell lymphoma (DLBCL), no apparent association between in vivo kinetics and response was noted, with a wide range of transgene levels at relapse. In B-ALL, patients with B-cell aplasia sustained >6 months had higher CAR T-cell expansion relative to those with early B-cell recovery (BCR) (<6 months after infusion); however, a definitive cutoff for BCR-associated expansion level could not be identified. In most patients with B-ALL, BCR >6 months maintained favorable responses. However, early BCR could not be confirmed as a potential indicator of relapse due to high censoring from transplant, following presumed risk of relapse. However, allografting in these patients may potentially mitigate the poor prognosis related to early BCR. In DLBCL, BCR was not associated with relapse. These findings suggest that blood CAR transgene levels may be associated with long-term responses; however, they lack robust predictive potential for relapses. As reported earlier, next-generation sequencing for minimal residual disease appears to be a reliable biomarker predictive of relapse for B-ALL.

Blood AdvancesVol. 9(17)
Intermountain Healthcare (US), Novartis (Switzerland) (CH), Hospital Sant Joan de Déu Barcelona (ES), St. Jude Children's Research Hospital (US), National Marrow Donor Program (US), Children's Mercy Hospital (US), Children's Hospital of Philadelphia (US), Emory University (US), Université Paris Cité (FR), University of Utah (US), University of Michigan (US), Peter MacCallum Cancer Centre (AU), Huntsman Cancer Institute (US), The Alfred Hospital (AU), Vienna General Hospital (AT), University of Chicago (US), Monash Alfred Psychiatry Research centre (AU), Assistance Publique – Hôpitaux de Paris (FR), The University of Kansas Cancer Center (US), Michigan United (US), Michigan Medicine (US), Novartis (United States) (US), Ann Arbor VA Medical Center (US), Hôpital Robert-Debré (FR), Sant Joan de Déu Research Foundation (ES), UPMC Hillman Cancer Center (US), University of Kansas Medical Center (US), University Hospital Cologne (DE), Tris Pharma (United States) (US), Medical University of Vienna (AT), University of Pennsylvania (US)
Amgen, Sanofi, Gilead Sciences, Celgene, Novartis Pharmaceuticals Corporation, CSL Behring, BeiGene, Incyte, Astellas Pharma, Servier, MorphoSys, Genentech, Kite Pharma, Juno Therapeutics, Novartis Institutes for BioMedical Research, Loxo Oncology, Legend Biotech, National Cancer Institute, Daiichi Sankyo Europe
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Openalex Percentile: Top 78%
CAR-T cell therapy research
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