High tumor burden before blinatumomab has a negative impact on the outcome of adult patients with B-cell precursor acute lymphoblastic leukemia. A real-world study by the GRAALL

Abstract

Blinatumomab is a bispecific T-cell engager approved for B-cell precursor acute lymphoblastic leukemia (B-ALL) with persistent minimal residual disease (MRD) or in relapse. The prognostic impact of tumor load has been suggested before other immunotherapies but remains poorly explored before blinatumomab. We retrospectively analyzed the outcome of 73 patients who received blinatumomab either in first complete remission (CR) with MRD+ (N=35) or at relapse (N=38). Among MRD+ patients, 91% had a MRD >0.01% before blinatumomab, and 89% achieved a complete MRD response after blinatumomab. High preblinatumomab MRD levels were associated with shorter RFS (p=0.049) and OS (p=0.011). At 3 years, OS was 33%, 58% and 86% for pre-blinatumomab MRD >1%, between 0.1-1%, and <0.1% respectively. Among relapsed patients, 23 received blinatumomab with overt relapse and 15 were in CR after bridging chemotherapy. At 3 years, overall CR rate was 68% and complete MRD response rate was 84%. Patients who directly received blinatumomab had shorter RFS (p=0.033) and OS (p=0.003) than patients bridged to blinatumomab. Three-year OS was 66% in the latter group compared to 16% in the former group. Our observations suggest that pre-blinatumomab tumor burden should help to design more tailored strategies including tumor load reduction in relapsed patients.