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Long-Term Follow-up of CD19 CAR Therapy in Acute Lymphoblastic Leukemia
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BACKGROUND: CD19-specific chimeric antigen receptor (CAR) T cells induce high rates of initial response among patients with relapsed B-cell acute lymphoblastic leukemia (ALL) and long-term remissions in a subgroup of patients. METHODS: We conducted a phase 1 trial involving adults with relapsed B-cell ALL who received an infusion of autologous T cells expressing the 19-28z CAR at the Memorial Sloan Kettering Cancer Center (MSKCC). Safety and long-term outcomes were assessed, as were their associations with demographic, clinical, and disease characteristics. RESULTS: A total of 53 adults received 19-28z CAR T cells that were manufactured at MSKCC. After infusion, severe cytokine release syndrome occurred in 14 of 53 patients (26%; 95% confidence interval [CI], 15 to 40); 1 patient died. Complete remission was observed in 83% of the patients. At a median follow-up of 29 months (range, 1 to 65), the median event-free survival was 6.1 months (95% CI, 5.0 to 11.5), and the median overall survival was 12.9 months (95% CI, 8.7 to 23.4). Patients with a low disease burden (<5% bone marrow blasts) before treatment had markedly enhanced remission duration and survival, with a median event-free survival of 10.6 months (95% CI, 5.9 to not reached) and a median overall survival of 20.1 months (95% CI, 8.7 to not reached). Patients with a higher burden of disease (≥5% bone marrow blasts or extramedullary disease) had a greater incidence of the cytokine release syndrome and neurotoxic events and shorter long-term survival than did patients with a low disease burden. CONCLUSIONS: In the entire cohort, the median overall survival was 12.9 months. Among patients with a low disease burden, the median overall survival was 20.1 months and was accompanied by a markedly lower incidence of the cytokine release syndrome and neurotoxic events after 19-28z CAR T-cell infusion than was observed among patients with a higher disease burden. (Funded by the Commonwealth Foundation for Cancer Research and others; ClinicalTrials.gov number, NCT01044069 .).
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“It has been reported that CAR-T cell therapy shows high response rates to B-ALL patients in different age groups [117–119].”
From Immunosenescence: a key player in cancer development (2020) · cites this paper as [119]
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Metadata
- Authors
- Park, J. H., Rivière, I., Gonen, M., Wang, X., Sénéchal, B., Curran, K. J., Sauter, C., Wang, Y., Santomasso, B., Mead, E., Roshal, M., Maslak, P., Davila, M., Brentjens, R. J., & Sadelain, M.
- Affiliations
- Memorial Sloan Kettering Cancer Center (US)
- From the Leukemia Service, Department of Medicine (J.H.P., C.S., P.M., R.J.B.), the Michael G. Harris Cell Therapy and Cell Engineering Facility (I.R., X.W., B. Sénéchal, Y.W.), the Center for Cell Engineering (J.H.P., I.R., X.W., R.J.B., M.S.), and the Departments of Epidemiology and Biostatistics (M.G.), Pediatrics (K.J.C.), Neurology (B. Santomasso), Anesthesiology and Critical Care Medicine (E.M.), and Pathology (M.R.), Memorial Sloan Kettering Cancer Center, and the Department of Medicine, Joan...
- ORCID
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2018-02
- Volume
- 378
- Issue
- 5
- Pages
- 449-459
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- PMC
- PMC6637939
- OpenAlex
- W2787621143
- Cited by
- 2,688
- References
- 24
- Citations by year
- 2026: 164 · 2025: 235 · 2024: 306 · 2023: 351 · 2022: 365 · 2021: 403 · 2020: 412 · 2019: 290 · 2018: 156
- FWCI
- 118.36
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Comprehensive Cancer Network Foundation (Young Investigator Award)
- Emerald Foundation
- National Institute of Health (R01CA138738-05, P01CA059350, P01CA190174-01)
- Leukemia and Lymphoma Society (Career Development Award)
- American Society of Clinical Oncology (Career Development Award)
- Memorial Sloan Kettering Cancer Center Support Grant (P30CA008748)
- Juno Therapeutics
- Center for Experimental Therapeutics at Memorial Sloan Kettering Cancer Center
- Stand Up To Cancer
- William Lawrence and Blanche Hughes Foundation
- Annual Terry Fox Run for Cancer Research
- Carson Family Charitable Trust
- Topics
- Health Sciences › Medicine › Oncology › CAR-T cell therapy research
- Health Sciences › Medicine › Hematology › Acute Lymphoblastic Leukemia research
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Keywords
- CD19 CAR T cells, B-cell acute lymphoblastic leukemia, relapsed leukemia, autologous T cell therapy, cytokine release syndrome, neurotoxicity, disease burden, bone marrow blasts, event-free survival, overall survival, long-term outcomes
- MeSH terms
- Adult, Aged, Follow-Up Studies, Humans, Middle Aged, Receptors, Antigen, T-Cell, Recurrence, Remission Induction, T-Lymphocytes, Survival Analysis, Cytokines, Precursor Cell Lymphoblastic Leukemia-Lymphoma
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