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

Carlos A. Ramos, Natalie S. Grover, Anne W. Beaven, Premal D. 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 L. McKay, Birju Mehta, Catherine J. Cheng, Faith B. Buchanan, Bambi J. Grilley, Kaitlin Morrison, Malcolm K. BrennerJonathan S. Serody, Gianpietro Dotti, Helen E. Heslop, Barbara Savoldo

Research output: Contribution to journalArticle

19 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)3794-3804
Number of pages11
JournalJournal of Clinical Oncology
Volume38
Issue number32
DOIs
StatePublished - Nov 10 2020

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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