B 细胞急性淋巴细胞白血病中 CD19 靶向治疗后 CD19 阴性复发的临床意义

CD19-directed therapy remains the mainstay treatment for relapsed/refractory B-cell acute lymphoblastic leukemia (ALL).

However, treatment patterns and outcomes following CD19-negative (CD19-) relapse remain poorly defined.

We retrospectively analyzed 65 adult patients with ALL who developed CD19-relapse after CD19-directed therapy. TP53 mutations and BCR::ABL1-like ALL were each identified in 27. 7% (n = 18) of patients. Forty-six patients (70. 8%) received one CD19-targeted therapy, whereas 19 patients (29. 2%) received 2 prior to CD19-relapse.

Overall, 60 patients (92. 3%) received blinatumomab, and 23 (35. 4%) received CAR T-cell therapy. The median time from the initiation of the most recent CD19-targeted therapy to CD19-relapse was 155 days (range, 13-1946). The median follow-up of the entire cohort was 32. 7 months (IQR, 15. 1-90. 3). The median event-free and overall survival (EFS and OS) was 3. 1 months (95% CI, 2. 5-4. 5) and 9. 9 months (95% CI, 6. 8-24. 7), respectively. In multivariate analysis, receipt of 2 CD19-directed therapies was associated with both inferior EFS and OS, HR 2.

17 (95% CI, 1. 10-4. 29; p = 0. 03) and HR 3. 05 (95% CI, 1. 40-6. 62; p = 0. 005). The complete remission rate following first salvage therapy was 47. 5% and 72. 1% any time following CD19-relapse. Sixteen (34. 8%) of 46 patients evaluated had subsequent CD19 re-expression, 5 of whom subsequently received CD19-directed therapy, and all 5 patients responded. Patients with ALL who develop CD19-relapse after CD19-directed therapy have poor outcomes and limited therapeutic options.

However, since this study lacked a comparator cohort of patients with CD19-positive relapse, the independent prognostic impact of CD19 negativity could not be determined.