Incipient clonal hematopoiesis is accelerated following CD30.CAR-T therapy
Copyright © 2023 International Society for Cell & Gene Therapy. Published by Elsevier Inc. All rights reserved..
Chimeric antigen receptor (CAR) T-cells are an emerging therapy for refractory lymphomas. Clonal hematopoiesis (CH), the preferential outgrowth of mutated bone marrow progenitors, is enriched in lymphoma patients receiving CAR-T cells. CAR-T therapy requires conditioning chemotherapy and often induces systemic inflammatory reactions, both of which have been shown to promote expansion of CH clones. Thus, we hypothesized that pre-existing CH clones could expand during CAR-T cell treatment. We measured CH at 154 timepoints longitudinally sampled from 26 patients receiving CD30.CAR-T therapy for CD30+ lymphomas on an investigational protocol (NCT02917083). Pre-treatment CH was present in 54% of individuals and did not correlate with survival outcomes or inflammatory toxicities. Longitudinal tracking of single clones in individual patients revealed distinct clone growth dynamics. Initially small clones, defined as VAF <1%, expanded following CAR-T administration, compared with relatively muted expansions of larger clones (3.37-fold vs. 1.20-fold, P = 0.0014). Matched clones were present at low magnitude in the infused CD30.CAR-T product for all CH cases but did not affect the product's immunophenotype or transduction efficiency. As cellular immunotherapies expand to become frontline treatments for hematological malignancies, our data indicates CAR-T recipients could be enriched for CH, and further longitudinal studies centered on CH complications in this population are warranted.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:26 |
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| Enthalten in: |
Cytotherapy - 26(2024), 3 vom: 26. März, Seite 261-265 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Kapadia, Chiraag D [VerfasserIn] |
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| Links: |
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| Themen: |
CAR-T |
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| Anmerkungen: |
Date Completed 26.02.2024 Date Revised 09.03.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.jcyt.2023.11.013 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 520 | |a Chimeric antigen receptor (CAR) T-cells are an emerging therapy for refractory lymphomas. Clonal hematopoiesis (CH), the preferential outgrowth of mutated bone marrow progenitors, is enriched in lymphoma patients receiving CAR-T cells. CAR-T therapy requires conditioning chemotherapy and often induces systemic inflammatory reactions, both of which have been shown to promote expansion of CH clones. Thus, we hypothesized that pre-existing CH clones could expand during CAR-T cell treatment. We measured CH at 154 timepoints longitudinally sampled from 26 patients receiving CD30.CAR-T therapy for CD30+ lymphomas on an investigational protocol (NCT02917083). Pre-treatment CH was present in 54% of individuals and did not correlate with survival outcomes or inflammatory toxicities. Longitudinal tracking of single clones in individual patients revealed distinct clone growth dynamics. Initially small clones, defined as VAF <1%, expanded following CAR-T administration, compared with relatively muted expansions of larger clones (3.37-fold vs. 1.20-fold, P = 0.0014). Matched clones were present at low magnitude in the infused CD30.CAR-T product for all CH cases but did not affect the product's immunophenotype or transduction efficiency. As cellular immunotherapies expand to become frontline treatments for hematological malignancies, our data indicates CAR-T recipients could be enriched for CH, and further longitudinal studies centered on CH complications in this population are warranted | ||
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| 700 | 1 | |a Wu, Mengfen |e verfasserin |4 aut | |
| 700 | 1 | |a Torrano, Virginia |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Tao |e verfasserin |4 aut | |
| 700 | 1 | |a Grilley, Bambi J |e verfasserin |4 aut | |
| 700 | 1 | |a Heslop, Helen E |e verfasserin |4 aut | |
| 700 | 1 | |a Ramos, Carlos A |e verfasserin |4 aut | |
| 700 | 1 | |a Goodell, Margaret A |e verfasserin |4 aut | |
| 700 | 1 | |a Lulla, Premal D |e verfasserin |4 aut | |
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