Anti-CD30 CAR-T Cell Therapy in Relapsed and Refractory Hodgkin Lymphoma

作者：Carlos A. Ramos, Natalie S. Grover, Anne Beaven, Premal Lulla, Meng-Fen Wu, Anastasia Ivanova, Tao Wang, Thomas C. Shea, Cliona M. Rooney, Christopher Dittus, Steven I. Park, Adrian P. Gee, Paul W. Eldridge, Kathryn McKay, Birju Mehta, Catherine Cheng, Faith Brianne Buchanan, Bambi Grilley, Kaitlin Morrison, Malcolm K. Brenner, Jonathan S. Serody, Gianpietro Dotti, Helen E. Heslop, Barbara Savoldo · 发表于：Journal of Clinical Oncology · 年份：2020 · DOI：10.1200/jco.20.01342 · 被引用次数：385 · 研究领域：CAR-T cell therapy research、Lymphoma Diagnosis and Treatment、Cutaneous lymphoproliferative disorders research

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 r...