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

Abstract

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.