Early Lymphopheresis May Improve CAR T-Cell Therapy in DLBCL

In patients with diffuse large B-cell lymphoma (DLBCL), early lymphopheresis for chimeric antigen receptor (CAR) T-cell therapy, ie, at first relapse before salvage treatment, leads to improved T-cell composition and functionality, a new study published in the British Journal of Haematology found.

The improved phenotype and function of T cells did not translate into clinical outcomes that were significantly better, but there was a trend towards better overall and progression-free survival among patients.

Read more about CAR T-cell therapies for DLBCL 

“Early lymphopheresis maximizes the potential of salvage therapies, without compromising CAR T-cell quality,” the authors of the study concluded. 

It is difficult to collect adequate and optimal T cells from patients with DLBCL because they have often been exposed to several lymphotoxic agents before T cells are harvested for CAR T-cell therapy. 

To identify potential ways to optimize the approach, a team of researchers led by Sigal Grisariu, MD, from the Faculty of Medicine, Department of Bone Marrow Transplantation and Cancer Immunotherapy, Hadassah Medical Center, Hebrew University of Jerusalem in Israel suggested starting the treatment earlier.

The team conducted a prospective study where they harvested T cells at the first relapse before salvage treatment was initiated in 22 patients with DLBCL and compared the clinical outcomes of CAR T-cell therapy with those of 23 patients who underwent standard lymphopheresis, ie, at the second relapse or later. 

They found that earlier lymphopheresis led to an increased percentage of naïve T cells compared to standard lymphopheresis. It also increased the functionality of T cells in vitro. Finally, T cells that were harvested earlier had a lower exhaustion profile than those collected later.

The team concluded that earlier lymphopheresis could improve the efficacy of CAR T-cell therapy in DLBCL. 

Reference

Dubnikov Sharon T, Assayag M, Avni B, et al. Early lymphocyte collection for anti-CD19 CART production improves T-cell fitness in patients with relapsed/refractory diffuse large B-cell lymphoma. Br J Haematol. Published online April 18, 2023. doi:10.1111/bjh.18816

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