复发/难治性 DLBCL 患者 CD19 CAR-T 治疗后的持续性血细胞减少或可预测疗效与不良反应

Hematological toxicity is a severe adverse event (AE) in anti-CD19 chimeric antigen receptor (CAR) T cell therapy for relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL).

However, the pathophysiological mechanism underlying prolonged cytopenia and the relationship between persistent cytopenia, efficacy, and AEs after anti-CD19 CAR T cell therapy are unknown.

Therefore, this study explored whether persistent cytopenia after anti-CD19 CAR T cell therapy in patients with R/R DLBCL can predict therapeutic efficacy and AEs. Thirty-eight patients with R/R DLBCL were enrolled in an anti-CD19 CAR T cell therapy clinical trial. Patients received lymphodepleting chemotherapy with fludarabine and cyclophosphamide before CAR T cell therapy. The degree and duration of cytopenia, clinical response, proportion of CAR T cells, interleukin-6 (IL-6) levels, AEs, and follow-up were observed after therapy. Grades 3-4 persistent cytopenia occurred in 14 patients with R/R DLBCL, who recovered 8-18 weeks after CAR T cell infusion.

These patients achieved an objective response rate (ORR) for anti-CD19 CAR T cell therapy. In patients who achieved ORR, the incidence of Grades 3-4 persistent cytopenia was higher in patients with a high tumor load than in those without a high tumor load.

The mean peaks of IL-6 and anti-CD19 CAR T cells and the cytokine release syndrome grade in patients with Grades 3-4 persistent cytopenia were higher than those in patients without persistent cytopenia. Anti-CD19 CAR T cells were observed 21 and 28 days after infusion, and patients had Grades 3-4 persistent cytopenia. Progression-free and overall survival were higher in patients with Grades 3-4 persistent cytopenia than in those without cytopenia.

Therefore, persistent cytopenia after anti-CD19 CAR T cell therapy in patients with R/R DLBCL can predict therapeutic efficacy and AEs, allowing clinicians to determine the efficiency of CD-19 CAR T cell therapy and the associated AEs.