CD3 cell count at the moment of leukapheresis could predict response to chimeric antigen receptor (CAR) T-cell therapy in patients with diffuse large B-cell lymphoma (DLBCL), thus aiding the development of therapeutic strategies, according to a recently published study in Scientific Reports.

Although DLBCL is curable with chemotherapy regimens based on anthracycline, an important percentage of patients do not respond to anthracycline. CAR T-cell therapy significantly improved the prognosis of this subgroup of patients, Fumiya Wada, of the Kyoto University in Japan, and colleagues reported.

However, the poor prognosis of patients with incomplete responses and the high risk of relapse have created a need for an adequate risk stratifying system, the study authors added.

Read more about DLBCL prognosis

Currently, prognostic factors for CAR T-cell therapy response are determined by tumor-specific factors such as tumor volume and genetic alterations. Therefore, the authors aimed to assess the prognostic value of a parameter unrelated to intrinsic tumor characteristics.

“In this study, we focused on the prognostic value of CD3+ cell count in peripheral blood at leukapheresis on outcomes of CAR T-cell therapy,” the authors wrote. 

The study included a cohort of 44 patients receiving treatment with tisagenlecleucel between 2019 and 2021. All of the included patients were refractory to 2 or more previous lines of treatment. To simplify risk stratification, patients were divided into a high CD3 and a low CD3 group. 

The study’s primary endpoint was progression-free survival (PFS), defined as the interval between the beginning of treatment and documented disease progression, relapse, or death. 

Results revealed that patients in the low CD3 group had a significantly worse 1-year PFS than the high CD3 group. Similarly, patients in the high CD3 group had significantly better overall survival than those in the low CD3 group, according to univariate analysis.

The cause of death was mainly relapse, with the exception of 2 patients that suffered from myelodysplastic syndrome and severe cytokine release syndrome.

Regarding the influence of CD3 cell count at leukapheresis on lymphocyte expansion after CAR T-cell infusion, CD3 counts at leukapheresis significantly correlated with increased lymphocyte counts in the first 7 days after infusion. An increased lymphocyte count at day 7 was associated with a better 1-year PFS.

“Optimizing CAR T-cell therapy at the time of leukapheresis, especially for high-risk patients, should be considered to achieve favorable CAR T-cell responses,” the authors concluded.

Reference

Wada F, Jo T, Arai Y, et al. T-cell counts in peripheral blood at leukapheresis predict responses to subsequent CAR-T cell therapy. Sci Rep. Published online November 4, 2022. doi:10.1038/s41598-022-23589-9