期刊
BLOOD
卷 134, 期 24, 页码 2149-2158出版社
AMER SOC HEMATOLOGY
DOI: 10.1182/blood.2019001463
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资金
- Stand Up to Cancer
- St. Baldrick's Pediatric Dream Team Translational Research Grant [SU2C-AACR-DT1113]
- National Institutes of Health, National Cancer Institute [R01 CA136551-05]
- Alex's Lemonade Stand Phase I/II Infrastructure Grant
- Conquer Cancer Foundation Career Development Award
- Washington State Life Sciences Discovery Fund
- Ben Towne Foundation
- William Lawrence & Blanche Hughes Foundation
- Juno Therapeutics, Inc., a Celgene company
Immunotherapy with the adoptive transfer of T cells redirected with CD19-specific chimeric antigen receptors (CARS) for B-lineage acute lymphoblastic leukemia (ALL) can salvage >80% of patients having relapsed/refractory disease. The therapeutic index of this emerging modality is attenuated by the occurrence of immunologic toxicity syndromes that occur upon CAR T-cell engraftment. Here, we report on the low incidence of severe cytokine release syndrome (CRS) in a subject treated with a CAR T-cell product composed of a defined ratio CD4:CD8 T-cell composition with a 4-1BB:zeta CAR targeting CD19 who also recieved early intervention treatment. We report that early intervention with tocilizumab and/or corticosteroids may reduce the frequency at which subjects transition from mild CRS to severe CRS. Although early intervention doubled the numbers of subjects dosed with tocilizumab and/or corticosteroids, there was no apparent detrimental effect on minimal residual disease-negative complete remission rates or subsequent persistence of functional CAR T cells compared with subjects who did not receive intervention. Moreover, early intervention therapy did not increase the proportion of subjects who experience neurotoxicity or place subjects at risk for infectious sequelae. These data support the contention that early intervention with tocilizumab and/or corticosteroids in subjects with early signs of CRS is without negative impact on the antitumor potency of CD19 CAR T cells. This intervention serves to enhance the therapeutic index in relapsed/ refractory patients and provides the rationale to apply CAR T-cell therapy more broadly in ALL therapy.
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