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Blood. 2016 Jun 16;127(24):2980-90. doi: 10.1182/blood-2015-12-686725. Epub 2016 Apr 26.

Phase 1 studies of central memory-derived CD19 CAR T-cell therapy following autologous HSCT in patients with B-cell NHL.

Author information

1
Department of Hematology and Hematopoietic Cell Transplantation.
2
Department of Information Sciences.
3
Clinical Trials Unit, and.
4
Department of Radiology, City of Hope, Duarte, CA;
5
Division of Pediatrics, University of Texas MD Anderson Cancer Center, Houston, TX;
6
Program in Immunology, Fred Hutchinson Cancer Research Center, Seattle, WA; and.
7
Ben Towne Center for Childhood Cancer Research, Seattle Children's Research Institute and School of Medicine, Seattle, WA.

Abstract

Myeloablative autologous hematopoietic stem cell transplantation (HSCT) is a mainstay of therapy for relapsed intermediate-grade B-cell non-Hodgkin lymphoma (NHL); however, relapse rates are high. In phase 1 studies designed to improve long-term remission rates, we administered adoptive T-cell immunotherapy after HSCT, using ex vivo-expanded autologous central memory-enriched T cells (TCM) transduced with lentivirus expressing CD19-specific chimeric antigen receptors (CARs). We present results from 2 safety/feasibility studies, NHL1 and NHL2, investigating different T-cell populations and CAR constructs. Engineered TCM-derived CD19 CAR T cells were infused 2 days after HSCT at doses of 25 to 200 × 10(6) in a single infusion. In NHL1, 8 patients safely received T-cell products engineered from enriched CD8(+) TCM subsets, expressing a first-generation CD19 CAR containing only the CD3ζ endodomain (CD19R:ζ). Four of 8 patients (50%; 95% confidence interval [CI]: 16-84%) were progression free at both 1 and 2 years. In NHL2, 8 patients safely received T-cell products engineered from enriched CD4(+) and CD8(+) TCM subsets and expressing a second-generation CD19 CAR containing the CD28 and CD3ζ endodomains (CD19R:28ζ). Six of 8 patients (75%; 95% CI: 35-97%) were progression free at 1 year. The CD4(+)/CD8(+) TCM-derived CD19 CAR T cells (NHL2) exhibited improvement in expansion; however, persistence was ≤28 days, similar to that seen by others using CD28 CARs. Neither cytokine release syndrome nor delayed hematopoietic engraftment was observed in either trial. These data demonstrate the safety and feasibility of CD19 CAR TCM therapy after HSCT. Trials were registered at www.clinicaltrials.gov as #NCT01318317 and #NCT01815749.

PMID:
27118452
PMCID:
PMC4911862
DOI:
10.1182/blood-2015-12-686725
[Indexed for MEDLINE]
Free PMC Article

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