Early lymphocyte collection for anti-CD19 CART production improves T-cell fitness in patients with relapsed/refractory diffuse large B-cell lymphoma

T. Dubnikov Sharon, M. Assayag, B. Avni, S. Kfir-Erenfeld, E. Lebel, M. E. Gatt, N. Goldschmidt, P. Stepensky*, N. Asherie*, S. Grisariu

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

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.

Original languageAmerican English
Pages (from-to)74-85
Number of pages12
JournalBritish Journal of Haematology
Volume202
Issue number1
DOIs
StatePublished - Jul 2023

Bibliographical note

Funding Information:
We would like to thank the patients and their families for participating in the study. We also would like to express our gratitude to the management board of directors of the Hadassah Medical Center for the ongoing support and its deep commitment to innovation. We also thank the staff in the clinical units for patient care, Mrs Avigail Avraham and Mrs Nassreen Hussein from the lymphopheresis unit. We also thank Prof. Ora Paltiel for her assistance in the statistical analyses. This work was supported by generous funding from Steinfeld and Cuniff family.

Publisher Copyright:
© 2023 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.

Keywords

  • CD19-CART
  • Lymphopheresis
  • T-cell fitness
  • relapsed/refractory diffuse large B-cell lymphoma

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