Obecabtagene Autoleucel in Adults with B-Cell Acute Lymphoblastic Leukemia

Claire Roddie; Karamjeet S Sandhu; Eleni Tholouli; Aaron C Logan; Paul Shaughnessy; Pere Barba; Armin Ghobadi; Manuel Guerreiro; Deborah Yallop; Mehrdad Abedi; Jeremy M Pantin; Jean A Yared; Amer M Beitinjaneh; Sridhar Chaganti; Katharine Hodby; Tobias Menne; Martha L Arellano; Ram Malladi; Bijal D Shah; Luke Mountjoy; Kristen M O'Dwyer; Karl S Peggs; Pierre Lao-Sirieix; Yiyun Zhang; Wolfram Brugger; Edgar Braendle; Martin Pule; Michael R Bishop; Daniel J DeAngelo; Jae H Park; Elias Jabbour

doi:10.1056/NEJMoa2406526

Obecabtagene Autoleucel in Adults with B-Cell Acute Lymphoblastic Leukemia

N Engl J Med. 2024 Nov 27. doi: 10.1056/NEJMoa2406526. Online ahead of print.

Authors

Claire Roddie¹, Karamjeet S Sandhu¹, Eleni Tholouli¹, Aaron C Logan¹, Paul Shaughnessy¹, Pere Barba¹, Armin Ghobadi¹, Manuel Guerreiro¹, Deborah Yallop¹, Mehrdad Abedi¹, Jeremy M Pantin¹, Jean A Yared¹, Amer M Beitinjaneh¹, Sridhar Chaganti¹, Katharine Hodby¹, Tobias Menne¹, Martha L Arellano¹, Ram Malladi¹, Bijal D Shah¹, Luke Mountjoy¹, Kristen M O'Dwyer¹, Karl S Peggs¹, Pierre Lao-Sirieix¹, Yiyun Zhang¹, Wolfram Brugger¹, Edgar Braendle¹, Martin Pule¹, Michael R Bishop¹, Daniel J DeAngelo¹, Jae H Park¹, Elias Jabbour¹

Affiliation

¹ 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.).

PMID: 39602653
DOI: 10.1056/NEJMoa2406526

Abstract

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.).

Associated data

ClinicalTrials.gov/NCT04404660