Roddie Claire, Sandhu Karamjeet S, Tholouli Eleni, Logan Aaron C, Shaughnessy Paul, Barba Pere, Ghobadi Armin, Guerreiro Manuel, Yallop Deborah, Abedi Mehrdad, Pantin Jeremy M, Yared Jean A, Beitinjaneh Amer M, Chaganti Sridhar, Hodby Katharine, Menne Tobias, Arellano Martha L, Malladi Ram, Shah Bijal D, Mountjoy Luke, O'Dwyer Kristen M, Peggs Karl S, Lao-Sirieix Pierre, Zhang Yiyun, Brugger Wolfram, Braendle Edgar, Pule Martin, Bishop Michael R, DeAngelo Daniel J, Park Jae H, Jabbour Elias
From the Cancer Institute, University College London (C.R., K.S.P., M.P.), University College London Hospitals NHS Foundation Trust (C.R.), King's College Hospital NHS Foundation Trust (D.Y.), and Autolus Therapeutics (P.L.-S., Y.Z., W.B., E.B., M.P.), London, Manchester Royal Infirmary, Manchester (E.T.), University Hospitals Birmingham NHS Foundation Trust, Birmingham (S.C.), University Hospitals Bristol NHS Foundation Trust, Bristol (K.H.), Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle (T.M.), and Cambridge University Hospitals NHS Foundation Trust, Cambridge (R.M.) - all in the United Kingdom; City of Hope National Medical Center, Duarte (K.S.S.), the Hematology, Blood and Marrow Transplant, and Cellular Therapy Program, University of California, San Francisco, San Francisco (A.C.L.), and UC Davis Medical Center, Sacramento (M.A.) - all in California; the Sarah Cannon Transplant and Cellular Therapy Program, Methodist Hospital, San Antonio (P.S.), and the University of Texas M.D. Anderson Cancer Center, Houston (E.J.) - both in Texas; Hospital Universitari Vall d'Hebron-Universitat Autónoma de Barcelona, Barcelona (P.B.), and Hospital Universitari i Politècnic La Fe, Valencia (M.G.) - both in Spain; Washington University School of Medicine, St. Louis (A.G.); the Sarah Cannon Transplant and Cellular Therapy Program, TriStar Centennial Medical Center, Nashville (J.M.P.); the University of Maryland Medical Center, Baltimore (J.A.Y.); Miller School of Medicine, University of Miami, Miami (A.M.B.), and Moffitt Cancer Center, Tampa (B.D.S.) - both in Florida; Winship Cancer Institute of Emory University, Atlanta (M.L.A.); Colorado Blood Cancer Institute, Denver (L.M.); the University of Rochester Medical Center, Rochester (K.M.O.), and Memorial Sloan Kettering Cancer Center, New York (J.H.P.) - both in New York; the David and Etta Jonas Center for Cellular Therapy, University of Chicago, Chicago (M.R.B.); and Dana-Farber Cancer Institute, Boston (D.J.D.).
N Engl J Med. 2024 Dec 12;391(23):2219-2230. doi: 10.1056/NEJMoa2406526. Epub 2024 Nov 27.
BACKGROUND: Obecabtagene autoleucel (obe-cel) is an autologous 41BB-ζ anti-CD19 chimeric antigen receptor (CAR) T-cell therapy which uses an intermediate-affinity CAR to reduce toxic effects and improve persistence. METHODS: We conducted a phase 1b-2 multicenter study of obe-cel in adults (≥18 years of age) with relapsed or refractory B-cell acute lymphoblastic leukemia (ALL). The main cohort, cohort 2A, included patients with morphologic disease; patients in cohort 2B had measurable residual disease. The primary end point was overall remission (complete remission or complete remission with incomplete hematologic recovery) in cohort 2A. Secondary end points included event-free survival, overall survival, and safety. RESULTS: Of the 153 enrolled patients, 127 (83.0%) received at least one infusion of obe-cel and were evaluable. In cohort 2A (94 patients; median follow-up, 20.3 months), overall remission occurred in 77% (95% confidence interval [CI], 67 to 85), with complete remission in 55% (95% CI, 45 to 66) and complete remission with incomplete hematologic recovery in 21% (95% CI, 14 to 31). The prespecified null hypotheses of overall remission (≤40%) and complete remission (≤20%) were rejected (P<0.001). In the 127 patients who received at least one obe-cel infusion (median follow-up, 21.5 months), the median event-free survival was 11.9 months (95% CI, 8.0 to 22.1); estimated 6- and 12-month event-free survival was 65.4% and 49.5%, respectively. The median overall survival was 15.6 months (95% CI, 12.9 to not evaluable); estimated 6- and 12-month overall survival was 80.3% and 61.1%, respectively. Grade 3 or higher cytokine release syndrome developed in 2.4% of the patients, and grade 3 or higher immune effector cell-associated neurotoxicity syndrome developed in 7.1% of the patients. CONCLUSIONS: Obe-cel resulted in a high incidence of durable response among adults with relapsed or refractory B-cell ALL, with a low incidence of grade 3 or higher immune-related toxic effects. (Funded by Autolus Therapeutics; FELIX ClinicalTrials.gov number, NCT04404660.).
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