{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T14:23:52Z","timestamp":1771338232976,"version":"3.50.1"},"reference-count":51,"publisher":"BMJ","issue":"2","license":[{"start":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T00:00:00Z","timestamp":1771286400000},"content-version":"unspecified","delay-in-days":16,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Center for Cancer Research, National Cancer Institute, NIH","award":["ZIABC011439-13"],"award-info":[{"award-number":["ZIABC011439-13"]}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Immunother Cancer"],"accepted":{"date-parts":[[2026,1,21]]},"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Cytokine-release syndrome (CRS) is a common toxicity of chimeric antigen receptor (CAR) T cells. CRS is often treated with corticosteroids such as dexamethasone. Dexamethasone is also used to treat multiple myeloma. To model CRS after CAR T-cell treatment of multiple myeloma (MM), three cell types are required: monocyte-lineage cells, CAR T cells, and MM cells. Some cytokines important in CRS, including interleukin (IL)-6, are released mainly by monocyte-lineage cells.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We added cells of an acute monocytic leukemia cell line (THP-1) to co-cultures of anti-B-cell maturation antigen (BCMA) CAR T cells (CAR-BCMA) and BCMA\n                      <jats:sup>+<\/jats:sup>\n                      target cells. Addition of THP-1 cells to the co-cultures led to increased levels of IL-6 and monocyte chemoattractant protein-1 (MCP-1) in culture supernatants. We developed a murine CRS model. This model included engraftment of THP-1 into NOD-scid common \u03b3-chain-deficient mice to provide a source of some cytokines associated with CRS, including IL-6 and MCP-1. The murine model also included engraftment of the bioluminescent BCMA\n                      <jats:sup>+<\/jats:sup>\n                      MM cell line MM.1S-veff-Luc and an infusion of CAR-BCMA. We treated CRS with dexamethasone or vehicle control.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      With this model, mice exhibited signs of CRS and had elevated serum cytokine levels after CAR T-cell infusion, and CAR-BCMA eliminated large burdens of MM.1S-veff-Luc. Dexamethasone administered 1, 3, and 5 days after CAR-BCMA ameliorated CRS. Dexamethasone was associated with faster elimination of MM burdens when either a dexamethasone-sensitive cell line (MM.1S-veff-Luc) or a dexamethasone-resistant cell line (MM.1R-veff-Luc) was used as the malignancy burden. Importantly, mice that received CAR-BCMA plus dexamethasone had higher levels of splenic CAR T cells when compared with mice that received CAR-BCMA without dexamethasone. When MM.1S-veff-Luc was treated, the median splenic CD3\n                      <jats:sup>+<\/jats:sup>\n                      CAR\n                      <jats:sup>+<\/jats:sup>\n                      cell count for mice that received CAR-BCMA plus dexamethasone was 764\u2009473 vs 327\u2009888 for mice that received CAR-BCMA without dexamethasone (p=0.0021).\n                    <\/jats:p>\n                    <jats:p>\n                      Among four patients who received anti-BCMA CAR T cells and corticosteroids on a clinical trial, CAR\n                      <jats:sup>+<\/jats:sup>\n                      cell levels continued to increase after initiation of corticosteroids in all patients.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In summary, our results should encourage further clinical research to design corticosteroid regimens that optimize treatment of CAR T-cell toxicities while maintaining anti-malignancy activity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration number<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT03602612\">NCT03602612<\/jats:ext-link>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/jitc-2025-012437","type":"journal-article","created":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T13:45:23Z","timestamp":1771335923000},"page":"e012437","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Corticosteroids ameliorate CAR T-cell-induced cytokine-release syndrome without inhibiting multiple myeloma 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USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Danielle A","family":"Natrakul","sequence":"additional","affiliation":[{"name":"Surgery Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jennifer N","family":"Brudno","sequence":"additional","affiliation":[{"name":"Surgery Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0723-2651","authenticated-orcid":false,"given":"Lauren C","family":"Cutmore","sequence":"additional","affiliation":[{"name":"Surgery Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, 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