期刊
BLOOD
卷 139, 期 7, 页码 1026-1038出版社
AMER SOC HEMATOLOGY
DOI: 10.1182/blood.2021012634
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资金
- National Institutes of Health (NIH) under Ruth L. Kirschstein National Research Service from the National Cancer Institute [T32CA009615]
- Lymphoma Research Foundation
- Stefan and Elizabeth Brodie Fund for Lymphoma Research at the University of Pennsylvania
- Lymphoma Research Foundation Career Development Awasr
- Gilead Research Scholar award
- Gabrielle's Angel Foundation
- Laffey-McHugh Foundation
- Parker Institute for Cancer Immunotherapy
- NIH, National Cancer Institute [1K99CA212302, R00CA212302]
- NIH [AI155577, AI082630, AI117950, CA210944]
- Berman and Maguire Funds for Lymphoma Research at the University of Pennsylvania
- Emerson Collective award
The use of PD1 inhibitor pembrolizumab after CD19-directed CAR T-cell therapy may be safe and achieve clinical responses in some patients with B-cell lymphomas refractory to or relapsed after CAR T-cell therapy.
CD19-directed chimeric antigen receptor-modified (CAR T) T cells achieve durable remissions in about 30% to 40% of relapsed/refractory large B-cell lymphomas. T-cell exhaustion and/or an immunosuppressive tumor microenvironment may contribute to CAR T-cell failure. Pembrolizumab, an anti-PD1 immune checkpoint inhibitor, may reverse T-cell exhaustion after CAR T-cell therapy. We treated 12 patients with B-cell lymphomas who were either refractory to (n = 9) or relapsed after (n = 3) CD19-directed CAR T-cell (4-1BB-costimulated) therapy with pembrolizumab 200 mg IV every 3 weeks. Median time from CAR T-cell infusion to first pembrolizumab dose was 3.3 months (range, 0.4-42.8 months). Pembrolizumab was well tolerated, and the only grade >3 adverse events related to pembrolizumab were neutropenia (n = 3; 25%). Best overall response rate after pembrolizumab was 25% (3 of 12 patients; 1 complete response; 2 partial responses). One (8%) patient had stable disease; thus, 4 of 12 (33%) patients had clinical benefit. After pembrolizumab, 4 patients with clinical benefit had an increase in percentage of CAR T cells by mass cytometry by time of flight (CyTOF); 3 of 4 of these patients also had increases in CAR19 transgene levels by quantitative polymerase chain reaction. Deep immune profiling using CyTOF revealed increased CAR T-cell activation and proliferation and less T-cell exhaustion in clinical responders. Together, PD1 blockade with pembrolizumab after CD19-directed CAR T-cell therapy appears safe and may achieve clinical responses in some patients with B-cell lymphomas refractory to or relapsed after CAR T-cell therapy.
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