Ramos et al. reported that a CD30-targeting CAR T cell (CD30.CART) infusion showed durable antitumor responses without significant toxicity in heavily treated patients with relapsed or refractory Hodgkin lymphoma. CD30.CARTs were well tolerated with limited grade 1 CRS and no neurological toxicity. In patients receiving fludarabine-based lymphodepletion and CD30.CART therapy, the ORR was 72%, including 59% CRs. PFS and OS after 1 year were 36% and 94%. CAR T cell expansion in vivo correlated with the initial dose, but didn’t predict clinical outcomes. Relapsing tumors retained CD30 expression.
Contributed by Shishir Pant
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 Info: (1) Center for Cell and Gene Therapy, Baylor College of Medicine, Houston Methodist Hospital and Texas Children's Hospital; Dan L. Duncan Cancer, Baylor College of Medicine; Housto
Author Info: (1) Center for Cell and Gene Therapy, Baylor College of Medicine, Houston Methodist Hospital and Texas Children's Hospital; Dan L. Duncan Cancer, Baylor College of Medicine; Houston, TX. Department of Medicine, Baylor College of Medicine, Houston, TX. (2) Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC. Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC. (3) Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC. Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC. (4) Center for Cell and Gene Therapy, Baylor College of Medicine, Houston Methodist Hospital and Texas Children's Hospital; Dan L. Duncan Cancer, Baylor College of Medicine; Houston, TX. Department of Medicine, Baylor College of Medicine, Houston, TX. (5) Center for Cell and Gene Therapy, Baylor College of Medicine, Houston Methodist Hospital and Texas Children's Hospital; Dan L. Duncan Cancer, Baylor College of Medicine; Houston, TX. Biostatistics Shared Resource, Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX. (6) Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC. Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, NC. (7) Center for Cell and Gene Therapy, Baylor College of Medicine, Houston Methodist Hospital and Texas Children's Hospital; Dan L. Duncan Cancer, Baylor College of Medicine; Houston, TX. Biostatistics Shared Resource, Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX. (8) Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC. Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC. (9) Center for Cell and Gene Therapy, Baylor College of Medicine, Houston Methodist Hospital and Texas Children's Hospital; Dan L. Duncan Cancer, Baylor College of Medicine; Houston, TX. Department of Pediatrics, Baylor College of Medicine, Houston, TX. Department of Pathology and Immunology, and Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX. (10) Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC. Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC. (11) Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC. (12) Center for Cell and Gene Therapy, Baylor College of Medicine, Houston Methodist Hospital and Texas Children's Hospital; Dan L. Duncan Cancer, Baylor College of Medicine; Houston, TX. Department of Pediatrics, Baylor College of Medicine, Houston, TX. (13) Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC. (14) Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC. (15) Center for Cell and Gene Therapy, Baylor College of Medicine, Houston Methodist Hospital and Texas Children's Hospital; Dan L. Duncan Cancer, Baylor College of Medicine; Houston, TX. (16) Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC. (17) Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC. (18) Center for Cell and Gene Therapy, Baylor College of Medicine, Houston Methodist Hospital and Texas Children's Hospital; Dan L. Duncan Cancer, Baylor College of Medicine; Houston, TX. (19) Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC. (20) Center for Cell and Gene Therapy, Baylor College of Medicine, Houston Methodist Hospital and Texas Children's Hospital; Dan L. Duncan Cancer, Baylor College of Medicine; Houston, TX. Department of Medicine, Baylor College of Medicine, Houston, TX. Department of Pediatrics, Baylor College of Medicine, Houston, TX. (21) Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC. Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC. Department of Immunology and Microbiology, University of North Carolina at Chapel Hill, Chapel Hill, NC. (22) Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC. Department of Immunology and Microbiology, University of North Carolina at Chapel Hill, Chapel Hill, NC. (23) Center for Cell and Gene Therapy, Baylor College of Medicine, Houston Methodist Hospital and Texas Children's Hospital; Dan L. Duncan Cancer, Baylor College of Medicine; Houston, TX. Department of Medicine, Baylor College of Medicine, Houston, TX. Department of Pediatrics, Baylor College of Medicine, Houston, TX. (24) Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC. Department of Immunology and Microbiology, University of North Carolina at Chapel Hill, Chapel Hill, NC. Department of Pediatrics, University of North Carolina at Chapel Hill, Chapel Hill, NC.
