{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T19:49:44Z","timestamp":1792180184571,"version":"4.4.0"},"reference-count":16,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"30","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["JCO"],"published-print":{"date-parts":[[2021,10,20]]},"abstract":"<jats:sec>\n                    <jats:title>PURPOSE<\/jats:title>\n                    <jats:p>Prognosis for adult B-cell acute lymphoblastic leukemia (B-ALL) is poor, and there are currently no licensed CD19 chimeric antigen receptor (CAR) therapeutics. We developed a novel second-generation CD19-CAR (CAT19-41BB-Z) with a fast off rate, designed for more physiologic T-cell activation to reduce toxicity and improve engraftment. We describe the multicenter phase I ALLCAR19 ( NCT02935257 ) study of autologous CAT19-41BB-Z CAR T cells (AUTO1) in relapsed or refractory (r\/r) adult B-ALL.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>Patients age \u2265 16 years with r\/r B-ALL were eligible. Primary outcomes were toxicity and manufacturing feasibility. Secondary outcomes were depth of response at 1 and 3 months, persistence of CAR-T, incidence and duration of hypogammaglobulinemia and B-cell aplasia, and event-free survival and overall survival at 1 and 2 years.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>Twenty-five patients were leukapheresed, 24 products were manufactured, and 20 patients were infused with AUTO1. The median age was 41.5 years; 25% had prior blinatumomab, 50% prior inotuzumab ozogamicin, and 65% prior allogeneic stem-cell transplantation. At the time of preconditioning, 45% had \u2265 50% bone marrow blasts. No patients experienced \u2265 grade 3 cytokine release syndrome; 3 of 20 (15%) experienced grade 3 neurotoxicity that resolved to \u2264 grade 1 within 72 hours with steroids. Seventeen of 20 (85%) achieved minimal residual disease\u2013negative complete response at month 1, and 3 of 17 underwent allogeneic stem-cell transplantation while in remission. The event-free survival at 6 and 12 months was 68.3% (42.4%-84.4%) and 48.3% (23.1%-69.7%), respectively. High-level expansion (Cmax 127,152 copies\/\u00b5g genomic DNA) and durable CAR-T persistence were observed with B-cell aplasia ongoing in 15 of 20 patients at last follow-up.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>AUTO1 demonstrates a tolerable safety profile, high remission rates, and excellent persistence in r\/r adult B-ALL. Preliminary data support further development of AUTO1 as a stand-alone treatment for r\/r adult B-ALL.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1200\/jco.21.00917","type":"journal-article","created":{"date-parts":[[2021,8,31]],"date-time":"2021-08-31T15:59:32Z","timestamp":1630425572000},"page":"3352-3363","update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":139,"title":["Durable Responses and Low Toxicity After Fast Off-Rate CD19 Chimeric Antigen Receptor-T Therapy in Adults With Relapsed or Refractory B-Cell Acute Lymphoblastic Leukemia"],"prefix":"10.1200","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4901-5858","authenticated-orcid":false,"given":"Claire","family":"Roddie","sequence":"first","affiliation":[{"name":"Cancer Institute, University College London, London, United Kingdom"},{"name":"Department of Haematology, UCLH, London, United 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