@article{ea126f9d06944508a8c76dfc2009623e,
title = "Anti-CD30 CAR-T Cell Therapy in Relapsed and Refractory Hodgkin Lymphoma",
abstract = "PURPOSE Chimeric antigen receptor (CAR) T-cell therapy of B-cell malignancies has proved to be effective. We show how the same approach of CAR T cells specific for CD30 (CD30.CAR-Ts) can be used to treat Hodgkin lymphoma (HL). METHODS We conducted 2 parallel phase I/II studies (ClinicalTrials.gov identifiers: NCT02690545 and NCT02917083) at 2 independent centers involving patients with relapsed or refractory HL and administered CD30.CAR-Ts after lymphodepletion with either bendamustine alone, bendamustine and fludarabine, or cyclophosphamide and fludarabine. The primary end point was safety. RESULTS Forty-one patients received CD30.CAR-Ts. Treated patients had a median of 7 prior lines of therapy (range, 2-23), including brentuximab vedotin, checkpoint inhibitors, and autologous or allogeneic stem cell transplantation. The most common toxicities were grade 3 or higher hematologic adverse events. Cytokine release syndrome was observed in 10 patients, all of which were grade 1. No neurologic toxicity was observed. The overall response rate in the 32 patients with active disease who received fludarabine-based lymphodepletion was 72%, including 19 patients (59%) with complete response. With a median follow-up of 533 days, the 1-year progression-free survival and overall survival for all evaluable patients were 36% (95% CI, 21% to 51%) and 94% (95% CI, 79% to 99%), respectively. CAR-T cell expansion in vivo was cell dose dependent. CONCLUSION Heavily pretreated patients with relapsed or refractory HL who received fludarabine-based lymphodepletion followed by CD30.CAR-Ts had a high rate of durable responses with an excellent safety profile, highlighting the feasibility of extending CAR-T cell therapies beyond canonical B-cell malignancies.",
author = "Ramos, {Carlos A.} and Grover, {Natalie S.} and Beaven, {Anne W.} and Lulla, {Premal D.} and Wu, {Meng Fen} and Anastasia Ivanova and Tao Wang and Shea, {Thomas C.} and Rooney, {Cliona M.} and Christopher Dittus and Park, {Steven I.} and Gee, {Adrian P.} and Eldridge, {Paul W.} and McKay, {Kathryn L.} and Birju Mehta and Cheng, {Catherine J.} and Buchanan, {Faith B.} and Grilley, {Bambi J.} and Kaitlin Morrison and Brenner, {Malcolm K.} and Serody, {Jonathan S.} and Gianpietro Dotti and Heslop, {Helen E.} and Barbara Savoldo",
note = "Funding Information: Supported at University of North Carolina (UNC) by Grant No. RO1 HL114564 and University Cancer Research Fund at the Lineberger Comprehensive Cancer Center, and at Baylor College of Medicine by National Cancer Institute Grants No. P50 CA126752 and P30 CA125123, and a Specialized Center of Research grant from the Leukemia & Lymphoma Society. N.S.G. was supported by UNC Oncology Grant No. K12 (K12 CA120780). We thank the patients who participated in these trials and their families. We also thank Todd Maguire, John West, Desirae Shelley, and the staff of the Lineberger Advanced Cellular Therapeutics Facility (University of North Carolina [UNC], Chapel Hill, NC); Huimin Zhang, Zhuyong Mei, Olga Dakhova and the staff of the Center for Cell and Gene Therapy facility (Baylor College of Medicine [BCM], Houston, TX); Spencer Laing, E. Samantha Sharf, Deborah Covington, and Maurice Alexander of the Cellular Therapeutic Program (UNC, Chapel Hill, NC), Mrinalini Bilgi and Vicky Torrano of the Center for Cell and Gene Therapy (BCM, Houston, TX) for help with clinical trial management; George Hucks (UNC, Chapel Hill, NC) and George Carrum and Rammurti Kamble (BCM, Houston, TX) for referring patients. We thank Dr Alessandro Rambaldi (Department of Oncology and Hematology, Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII, Bergamo, Italy) for the critical revision of the manuscript. We thank Bambi J. Grilley, Kaitlin Morrison for their contribution to regulatory support. We also thank Kenneth Cornetta and the National Gene Vector Biorepository at the Indiana University School of Medicine for postinfusion testing of the product for replication-competent retrovirus, the data and safety monitoring board, and the hematology-oncology and critical care faculty for providing clinical support; and the nurses, residents, and fellows at the 2 institutions. Funding Information: Supported at University of North Carolina (UNC) by Grant No. RO1 HL114564 and University Cancer Research Fund at the Lineberger Comprehensive Cancer Center, and at Baylor College of Medicine by National Cancer Institute Grants No. P50 CA126752 and P30 CA125123, and a Specialized Center of Research grant from the Leukemia & Lymphoma Society. N.S.G. was supported by UNC Oncology Grant No. K12 (K12 CA120780). Publisher Copyright: Copyright {\textcopyright} 2020 American Society of Clinical Oncology. All rights reserved.",
year = "2020",
month = nov,
day = "10",
doi = "10.1200/JCO.20.01342",
language = "English (US)",
volume = "38",
pages = "3794--3804",
journal = "Journal of Clinical Oncology",
issn = "0732-183X",
number = "32",
}