Allogeneic off-the-shelf CAR T-cell therapy for relapsed or refractory B-cell malignancies Journal Article
| Authors: | Shahid, S.; Prockop, S. E.; Flynn, G. C.; Mauguen, A.; White, C. O.; Bieler, J.; McAvoy, D.; Hosszu, K.; Cancio, M. I.; Jakubowski, A. A.; Scaradavou, A.; Boelens, J. J.; Sauter, C. S.; Perales, M. A.; Giralt, S. A.; Taylor, C.; Chaudhari, J.; Wang, X.; Rivière, I.; Sadelain, M.; Brentjens, R. J.; Kernan, N. A.; O’Reilly, R. J.; Curran, K. J. |
| Article Title: | Allogeneic off-the-shelf CAR T-cell therapy for relapsed or refractory B-cell malignancies |
| Abstract: | Despite clinical benefit with the use of chimeric antigen receptor (CAR) T cells, the need to manufacture patient-specific products limits its clinical utility. To overcome this barrier, we developed an allogeneic “off-the-shelf” CAR T-cell product using Epstein-Barr virus (EBV)–specific T cells (EBV-VSTs) genetically modified with a CD19-specific CAR (19-28z). Patients with relapsed/refractory (R/R) B-cell malignancies were stratified into 3 treatment cohorts: cohort 1 (n = 8; disease recurrence after allogeneic or autologous hematopoietic cell transplantation [HCT]), cohort 2 (n = 6; consolidative therapy after autologous HCT), or cohort 3 (n = 2; consolidative therapy after allogeneic HCT). The primary objective of this trial was to determine the safety of multiple CAR EBV-VST infusions. Most patients (n = 12/16) received multiple doses (overall median, 2.5 [range, 1-3]) with 3 × 106 T cells per kg determined to be the optimal dose enabling multiple treatments per manufactured cell line. Severe cytokine release syndrome or neurotoxicity did not occur after infusion, and no dose-limiting toxicity was observed in the trial. Median follow-up was 48 months (range, 4-135) with 4 deaths due to disease progression. Overall survival of all patients was 81% at 12 months and 75% at 36 months. Postinfusion expansion and persistence were limited, and CAR EBV-VSTs demonstrated a unique T-cell phenotype compared with autologous 19-28z CAR T cells. Our study demonstrates the feasibility and safety of an allogeneic “off-the-shelf” CAR EBV-VST product with favorable outcomes for patients with CD19+ R/R B-cell malignancies. This trial was registered at www.ClinicalTrials.gov as #NCT01430390. © 2025 American Society of Hematology. |
| Keywords: | adolescent; adult; child; clinical article; controlled study; treatment outcome; aged; survival rate; overall survival; neutropenia; chemotherapy; flow cytometry; neurotoxicity; polymerase chain reaction; thrombocytopenia; cohort analysis; cyclophosphamide; steroid; hematologic malignancy; hematopoietic cell; cell therapy; drug toxicity; seizure; hematopoietic stem cell; phase 1 clinical trial; immunosuppressive treatment; chronic lymphatic leukemia; marginal zone lymphoma; disease exacerbation; burkitt lymphoma; cell transplantation; hematopoietic cell transplantation; dose limiting toxicity; organ transplantation; cytokine release syndrome; diffuse large b cell lymphoma; human; article; b cell acute lymphoblastic leukemia; lymphodepleting chemotherapy; allogeneic off the shelf chimeric antigen receptor t cell therapy; refractory b cell malignancy; relapsed b cell malignancy |
| Journal Title: | Blood Advances |
| Volume: | 9 |
| Issue: | 7 |
| ISSN: | 2473-9529 |
| Publisher: | American Society of Hematology |
| Date Published: | 2025-04-08 |
| Start Page: | 1644 |
| End Page: | 1657 |
| Language: | English |
| DOI: | 10.1182/bloodadvances.2024015157 |
| PUBMED: | 39908482 |
| PROVIDER: | scopus |
| PMCID: | PMC11995077 |
| DOI/URL: | |
| Notes: | Article -- MSK Cancer Center Support Grant (P30 CA008748) acknowledged in PDF -- MSK corresponding author is Kevin Curran -- Source: Scopus |
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