{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T13:09:56Z","timestamp":1780664996457,"version":"3.54.1"},"reference-count":31,"publisher":"BMJ","issue":"6","license":[{"start":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T00:00:00Z","timestamp":1780617600000},"content-version":"unspecified","delay-in-days":4,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"name":"NIH Clinical Center, National Institutes of Health","award":["ZIA BC 011823"],"award-info":[{"award-number":["ZIA BC 011823"]}]},{"name":"Intramural Research Program, Center of Cancer Research, National Cancer Institute","award":["ZIA BC 011823"],"award-info":[{"award-number":["ZIA BC 011823"]}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Immunother Cancer"],"accepted":{"date-parts":[[2026,5,21]]},"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:p>\n                    Multiantigen targeting chimeric antigen receptor (CAR) T cells have emerged as a strategy to mitigate antigen escape observed after single antigen targeting therapy. Our initial experience with a bivalent CD19.22.BB\u03b6 CAR T-cell construct in children, adolescents and young adults (CAYA) with B-cell acute lymphoblastic leukemia (B-ALL) demonstrated limitations in CD22 recognition, but a tolerable safety profile and efficacy prompted further evaluation. This trial enrolled patients between the ages of 3\u201339 with relapsed\/refractory B-ALL. Following dose-escalation, patients who enrolled at the recommended phase 2 dose (RP2D) of 3\u00d710\n                    <jats:sup>6<\/jats:sup>\n                    transduced CAR T cells\/kg constitute this report. 30 CAYA were treated at the RP2D; 28 with B-ALL and 2 with Burkitt lymphoma. Across patients with B-ALL, 20 (71.4%) patients developed cytokine release syndrome (CRS); only 2 (10%) were grade\n                    <jats:underline>&gt;<\/jats:underline>\n                    3. Grade 3 immune effector cell-associated neurotoxicity syndrome (ICANS) occurred in 3 (10.7%) patients; there were no cases of immune effector cell-associated hemophagocytic lymphohistiocytosis-like syndrome. Following a protocol amendment to evaluate the efficacy of siltuximab as a first-line treatment of CRS, one patient received siltuximab with full resolution of CRS after two doses without needing additional anti-cytokine-directed therapies. A measurable residual disease-negative complete remission (CR) was attained in 25 (89.3%) patients, including 6 who had neither CRS nor ICANS. 23 patients (82.1%) proceeded directly to hematopoietic stem cell transplant (HSCT) following CAR T-cell infusion within a median of 51 days (range, 45\u201368\u2009days), supporting the utility of this construct as a bridge to HSCT. All three non-responders had persistent non-central nervous system (CNS) extramedullary disease (EMD), although four of seven patients with non-CNS EMD achieved a CR. Median relapse-free survival among the 25 patients achieving CR was not reached, and the median overall survival for all 28 patients was 34 months (95%\u2009CI 17 to not estimable) from infusion. This extended experience demonstrates that CD19.22.BB\u03b6 CAR T-cell therapy is safe and clinically active, particularly as a bridge to HSCT. Non-response was confined to patients with non-CNS EMD, highlighting the persistent challenge of effectively targeting EMD and informing the design of future CAR constructs.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Trial registration number<\/jats:bold>\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT03448393\">NCT03448393<\/jats:ext-link>\n                    .\n                  <\/jats:p>","DOI":"10.1136\/jitc-2026-015296","type":"journal-article","created":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T12:35:11Z","timestamp":1780662911000},"page":"e015296","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["CD19\/CD22 bivalent CAR T cells in children, adolescents and young adults with B-ALL: final phase 1 trial results"],"prefix":"10.1136","volume":"14","clinical-trial-number":[{"clinical-trial-number":"nct03448393","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct03448393","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct05442515","registry":"10.18810\/clinical-trials-gov"}],"author":[{"given":"Sara K.","family":"Silbert","sequence":"first","affiliation":[{"name":"Pediatric Oncology Branch, National Cancer Institute, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Flavia","family":"Gava","sequence":"additional","affiliation":[{"name":"Pediatric Oncology Branch, National Cancer Institute, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bonnie","family":"Yates","sequence":"additional","affiliation":[{"name":"Pediatric Oncology Branch, National Cancer Institute, Bethesda, Maryland, USA"},{"name":"University of Colorado Denver Children\u2019s Hospital Colorado 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USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michaela","family":"Prochazkova","sequence":"additional","affiliation":[{"name":"Center for Cellular Engineering, National Institutes of Health, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren","family":"Little","sequence":"additional","affiliation":[{"name":"Pediatric Oncology Branch, National Cancer Institute, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toni","family":"Foley","sequence":"additional","affiliation":[{"name":"Pediatric Oncology Branch, National Cancer Institute, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hari","family":"Sankaran","sequence":"additional","affiliation":[{"name":"Biometric Research Program, National Cancer Institute, Bethesda, Maryland, 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