Blinatumomab for minimal residual disease in adults with B-precursor acute lymphoblastic leukemia.

Approximately 30-50% of adults with acute lymphoblastic leukemia (ALL) in hematologic complete remission following multiagent therapy exhibit minimal residual disease (MRD) by reverse transcriptase-polymerase chain reaction or flow cytometry. MRD is the strongest predictor of relapse in ALL. In this open-label, single-arm study, adults with B-cell precursor ALL in hematologic complete remission with MRD (≥10-3) received blinatumomab 15 µg/m2/day by continuous intravenous infusion for up to four cycles. Patients could undergo allogeneic hematopoietic stem cell transplantation any time after cycle 1. The primary endpoint was complete MRD response status after one cycle of blinatumomab. One hundred sixteen patients received blinatumomab. Eighty-eight of 113 evaluable patients (78%) achieved a complete MRD response. In the subgroup of 110 patients with Philadelphia-chromosome negative ALL in hematologic remission, the Kaplan-Meier estimate of relapse-free survival (RFS) at 18 months was 53%. Median overall survival was 36.5 months. In a landmark analysis, complete MRD responders had longer relapse-free survival (23.6 vs 5.7 months; P=0.002) and overall survival (OS) (38.9 vs 12.5 months; P=0.002) compared with MRD nonresponders. Adverse events were consistent with previous studies of blinatumomab. Twelve (10%) patients and three (3%) patients had grade 3 or 4 neurologic events, respectively. Four (3%) patients had cytokine release syndrome (two grade 1 and two grade 3), all during cycle 1. Following treatment with blinatumomab in a population of patients with MRD-positive B-cell precursor ALL, the majority achieved a complete MRD response, which was associated with significantly longer RFS and OS compared with MRD nonresponders. The study is registered to https://clinicaltrials.gov as NCT01207388.