Early lymphocyte collection for anti‐CD19 CART production improves T‐cell fitness in patients with relapsed/refractory diffuse large B‐cell lymphoma
Summary Background Chimeric antigen receptor (CAR) T cells targeted to the CD19 B‐cell antigen form an approved treatment for patients with relapsed/refractory diffuse large B‐cell lymphoma (r/r DLBCL). However, since this therapy is administered after multiple lines of treatment and exposure to lym...
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| Published in: | British journal of haematology Vol. 202; no. 1; pp. 74 - 85 |
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| Main Authors: | , , , , , , , , , |
| Format: | Journal Article |
| Language: | English |
| Published: |
England
Blackwell Publishing Ltd
01-07-2023
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| Subjects: | |
| Online Access: | Get full text |
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Background
Chimeric antigen receptor (CAR) T cells targeted to the CD19 B‐cell antigen form an approved treatment for patients with relapsed/refractory diffuse large B‐cell lymphoma (r/r DLBCL). However, since this therapy is administered after multiple lines of treatment and exposure to lymphotoxic agents, there is an urgent need to optimize this modality of treatment.
Methods
To circumvent the difficulties of harvesting adequate and optimal T cells from DLBCL patients and improve CART therapy, we suggest an earlier lymphopheresis (i.e. at first relapse, before salvage treatment). We conducted a prospective study and evaluated the potential benefit of an earlier lymphopheresis (early group, n = 22) on the clinical outcome of CD19‐CART infused DLBCL patients, in comparison with standard lymphopheresis (i.e. at second relapse and beyond; standard group, n = 23).
Results
An increased percentage of naïve T cells and increased in vitro T‐cell functionality were observed in the early group. Additionally, these cells exhibit a lower exhaustion profile than T cells collected in the standard group.
Conclusion
While improved T‐cell phenotype and function in the lymphopheresis product did not translate into significantly improved clinical outcomes, a trend towards better overall survival (OS) and progression‐free survival (PFS) was observed. Early lymphopheresis maximizes the potential of salvage therapies, without compromising CAR T‐cell quality. |
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| Bibliography: | T. Dubnikov Sharon and M. Assayag contributed equally to this work. P. Stepensky, N. Asherie and S. Grisariu contributed equally to this work. ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
| ISSN: | 0007-1048 1365-2141 |
| DOI: | 10.1111/bjh.18816 |