Clinical Implications of CD19-Negative Relapse Following CD19-Directed Therapy in B-Cell Acute Lymphoblastic Leukemia

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.