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dc.contributor.authorRoddie, C.
dc.contributor.authorDias, J.
dc.contributor.authorO'Reilly, M. A.
dc.contributor.authorAbbasian, M.
dc.contributor.authorCadinanos-Garai, A.
dc.contributor.authorVispute, K.
dc.contributor.authorBosshard-Carter, L.
dc.contributor.authorMitsikakou, M.
dc.contributor.authorMehra, V.
dc.contributor.authorRoddy, H.
dc.contributor.authorHartley, J. A.
dc.contributor.authorSpanswick, V.
dc.contributor.authorLowe, H.
dc.contributor.authorPopova, B.
dc.contributor.authorClifton-Hadley, L.
dc.contributor.authorWheeler, G.
dc.contributor.authorOlejnik, J.
dc.contributor.authorBloor, Adrian
dc.contributor.authorIrvine, D.
dc.contributor.authorWood, L.
dc.contributor.authorMarzolini, M. A. V.
dc.contributor.authorDomning, S.
dc.contributor.authorFarzaneh, F.
dc.contributor.authorLowdell, M. W.
dc.contributor.authorLinch, D. C.
dc.contributor.authorPule, M. A.
dc.contributor.authorPeggs, K. S.
dc.date.accessioned2021-09-30T11:56:00Z
dc.date.available2021-09-30T11:56:00Z
dc.date.issued2021en
dc.identifier.citationRoddie C, Dias J, O’Reilly MA, Abbasian M, Cadinanos-Garai A, Vispute K, et al. 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. JCO. 2021 Aug 31;JCO.21.00917.en
dc.identifier.pmid34464155en
dc.identifier.doi10.1200/jco.21.00917en
dc.identifier.urihttp://hdl.handle.net/10541/624589
dc.description.abstractPurpose: 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. Methods: Patients age ≥ 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. Results: 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 ≥ 50% bone marrow blasts. No patients experienced ≥ grade 3 cytokine release syndrome; 3 of 20 (15%) experienced grade 3 neurotoxicity that resolved to ≤ grade 1 within 72 hours with steroids. Seventeen of 20 (85%) achieved minimal residual disease-negative 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/µg genomic DNA) and durable CAR-T persistence were observed with B-cell aplasia ongoing in 15 of 20 patients at last follow-up. Conclusion: 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.en
dc.language.isoenen
dc.relation.urlhttps://dx.doi.org/10.1200/jco.21.00917en
dc.titleDurable responses and low toxicity after fast off-rate CD19 chimeric antigen receptor-t therapy in adults with relapsed or refractory b-cell acute lymphoblastic leukemiaen
dc.typeArticleen
dc.contributor.departmentCancer Institute, University College London, London, United Kingdomen
dc.identifier.journalJournal of Clinical Oncologyen
dc.description.noteen]
refterms.dateFOA2021-10-13T07:33:38Z


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