T-cell counts in peripheral blood at leukapheresis predict responses to subsequent CAR-T cell therapy
Fumiya Wada, Tomoyasu Jo, Yasuyuki Arai, Toshio Heike, Chisaki Mizumoto, Junya Kanda, Momoko Nishikori, Kouhei Yamashita, Miki Nagao, Akifumi Takaori‐Kondo
Abstract
Abstract 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/μL, 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/μL, 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.