白细胞分离时外周血 T 细胞计数预测后续 CAR-T 细胞治疗应答

Prediction of responses to chimeric antigen receptor (CAR)-T cell therapies is essential to maximize their therapeutic efficacy for diffuse large B-cell lymphoma (DLBCL). While several tumor-intrinsic risk factors of resistance and/or early relapse have been identified, clinically useful markers that determine potential activity of CAR-T cells have not been fully investigated. T-cell property at the time of leukapheresis may serve as such a marker.

Therefore, we evaluated the clinical impact of CD3 + cell count in peripheral blood at leukapheresis on clinical outcomes of CAR-T cell therapy. In total, 44 patients with relapsed or refractory (r/r) DLBCL who received tisagenlecleucel at Kyoto University Hospital were included.

According to CD3 + cell counts, patients were categorized into CD3 LOW and CD3 HIGH groups with a threshold of 553/ L, based on receiver operating characteristic curve analysis. 1-year progression-free survival was significantly higher in the CD3 HIGH group than the CD3 LOW group (68. 3% vs. 17. 3%; adjusted hazard ratio [aHR], 0. 37; p = 0. 042).

Overall survival was also superior in the CD3 HIGH group (aHR, 0. 24; p = 0. 043).

Moreover, higher CD3 + cell counts at leukapheresis were associated with significantly higher lymphocyte counts in peripheral blood at day 7 after CAR-T cell infusion (median 860 vs. 420/ L, P = 0. 021), suggesting more extensive expansion of infused CAR-T cells in vivo.

In conclusion, we demonstrated that the CD3 + cell count at leukapheresis predicts both expansion of CAR-T cells after infusion and outcomes of CAR-T cell therapy, and are useful for building comprehensive therapeutic strategies at the time of leukapheresis.