Journal article
Axicabtagene Ciloleucel CAR T-Cell Therapy in Refractory Large B-Cell Lymphoma
The New England journal of medicine, Vol.377(26), pp.2531-2544
12/28/2017
DOI: 10.1056/NEJMoa1707447
PMCID: PMC5882485
PMID: 29226797
Abstract
In a phase 1 trial, axicabtagene ciloleucel (axi-cel), an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, showed efficacy in patients with refractory large B-cell lymphoma after the failure of conventional therapy.
In this multicenter, phase 2 trial, we enrolled 111 patients with diffuse large B-cell lymphoma, primary mediastinal B-cell lymphoma, or transformed follicular lymphoma who had refractory disease despite undergoing recommended prior therapy. Patients received a target dose of 2×10
anti-CD19 CAR T cells per kilogram of body weight after receiving a conditioning regimen of low-dose cyclophosphamide and fludarabine. The primary end point was the rate of objective response (calculated as the combined rates of complete response and partial response). Secondary end points included overall survival, safety, and biomarker assessments.
Among the 111 patients who were enrolled, axi-cel was successfully manufactured for 110 (99%) and administered to 101 (91%). The objective response rate was 82%, and the complete response rate was 54%.With a median follow-up of 15.4 months, 42% of the patients continued to have a response, with 40% continuing to have a complete response. The overall rate of survival at 18 months was 52%. The most common adverse events of grade 3 or higher during treatment were neutropenia (in 78% of the patients), anemia (in 43%), and thrombocytopenia (in 38%). Grade 3 or higher cytokine release syndrome and neurologic events occurred in 13% and 28% of the patients, respectively. Three of the patients died during treatment. Higher CAR T-cell levels in blood were associated with response.
In this multicenter study, patients with refractory large B-cell lymphoma who received CAR T-cell therapy with axi-cel had high levels of durable response, with a safety profile that included myelosuppression, the cytokine release syndrome, and neurologic events. (Funded by Kite Pharma and the Leukemia and Lymphoma Society Therapy Acceleration Program; ZUMA-1 ClinicalTrials.gov number, NCT02348216 .).
Details
- Title: Subtitle
- Axicabtagene Ciloleucel CAR T-Cell Therapy in Refractory Large B-Cell Lymphoma
- Creators
- Sattva S Neelapu - The University of Texas Health Science Center at HoustonFrederick L Locke - University of South FloridaNancy L Bartlett - Washington University in St. LouisLazaros J Lekakis - University of Miami*David B Miklos - Stanford UniversityCaron A Jacobson - Dana-Farber Cancer InstituteIra Braunschweig - Yeshiva UniversityOlalekan O Oluwole - Vanderbilt UniversityTanya Siddiqi - City Of Hope National Medical CenterYi Lin - Mayo Clinic Rochester, MNJohn M Timmerman - University of California, Los AngelesPatrick J Stiff - Loyola University ChicagoJonathan W Friedberg - University of RochesterIan W Flinn - Sarah Cannon Research InstituteAndre Goy - Rutgers, The State University of New JerseyBrian T Hill - Cleveland ClinicMitchell R Smith - Cleveland ClinicAbhinav Deol - Wayne State UniversityUmar Farooq - University of IowaPeter McSweeney - Colorado Blood Cancer InstituteJavier Munoz - MD Anderson Cancer Center MadridIrit Avivi - Tel Aviv UniversityJanuario E Castro - University of California, San DiegoJason R Westin - The University of Texas Health Science Center at HoustonJulio C Chavez - University of South FloridaArmin Ghobadi - Washington University in St. LouisKrishna V Komanduri - University of Miami*Ronald Levy - Stanford UniversityEric D JacobsenThomas E Witzig - Mayo Clinic in FloridaPatrick Reagan - University of RochesterAdrian Bot - KiteJohn Rossi - KiteLynn Navale - KiteYizhou Jiang - KiteJeff Aycock - KiteMeg Elias - KiteDavid Chang - KiteJeff Wiezorek - KiteWilliam Y Go - Kite
- Resource Type
- Journal article
- Publication Details
- The New England journal of medicine, Vol.377(26), pp.2531-2544
- DOI
- 10.1056/NEJMoa1707447
- PMID
- 29226797
- PMCID
- PMC5882485
- ISSN
- 0028-4793
- eISSN
- 1533-4406
- Grant note
- P30 CA016672 / NCI NIH HHS
- Language
- English
- Date published
- 12/28/2017
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
- Record Identifier
- 9984360053602771
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