Peripheral blood B-cell early regeneration predicts clinical relapse and guides preemptive therapy after CAR-T treatment in acute lymphoblastic leukemia

Abstract

Abstract Background: Relapsed/refractory acute B lymphoblastic leukemia (R/R B-ALL) has a poor prognosis and low overall survival rate. Some patients experience rapid clinical relapse after achieving complete remission (CR) with chimeric antigen receptor T-cell (CAR-T) treatment. Therefore, predicting clinical relapse and implementing preemptive therapy after CAR-T treatment is of great significance for improving patient prognosis. Methods: The clinical data of 55 patients with R/R B-ALL who received CD19 CAR-T treatment were retrospectively analyzed. Survival analysis was conducted on peripheral blood B-cell count, bone marrow minimal residual disease (MRD), bone marrow CAR gene copy number, and the choice of preemptive therapy in patients who achieved CR. Results: The CR rate among 55 R/R B-ALL patients who received CD19 CAR-T treatment was 81.8%. For patients achieving CR, the median relapse-free survival was 290 days (95% CI 163-416), and the median overall survival was 870 days (95% CI 656-1084). All patients who achieved CR exhibited undetectable peripheral blood B-cell counts (0/μL) following CAR-T treatment. Survival analysis demonstrated that clinical relapse was highly correlated with peripheral blood B-cell early regeneration (within 45 days post-CAR-T infusion, but not after 45 days post-CAR-T infusion) (p<0.01), and was not associated with bone marrow MRD positivity or loss of CAR-T copy number at the same time. Furthermore, when peripheral blood B-cell early regeneration occurred, the choice of preemptive anti-leukemia therapy (including chemotherapy, targeted agents, or secondary CAR-T infusion) resulted in a significantly better relapse-free survival compared to immunomodulatory therapy (including interferon, interleukin-2) (p<0.05). Conclusion: B-cell early regeneration within 45 days after CD19 CAR-T treatment highly predicts clinical relapse in R/R B-ALL patients. Initiating anti-leukemic therapy promptly upon B-cell early regeneration can significantly extend relapse-free survival. This work was supported by grants from General Projects of Natural Science Foundation of Anhui Province (No.2208085MH217) and Anhui Clinical Medical Research and Translational Project (No.202427b10020036).