Efficacy and Toxicity of Blinatumomab in the French Compassionate Use Program (ATU) for Adult Patients With B-cell Precursor Acute Lymphoblastic Leukemia (BCP-ALL) Refractory, in Relapse, or With Positive Minimal Residual Disease.

The outcome of young adults (18-60 years) with ALL has been dramatically improved by the use of pediatric-inspired trials. About 60% of these young adult patients will be cured at 5 years. In this context, early evaluation of minimal residual disease (MRD) at complete remission has been shown to be one of the most powerful prognostic factor, but also predictive of the benefit of allogeneic stem cell transplantation (ASCT). Despite this global improvement, about 30% of patients experience a relapse and will be exposed to be refractory to salvage therapy or to early disease escape. In adult ALL, the most important prognostic factors at relapse are : the time from first CR to relapse, the achievement of a second complete remission (CR), and the feasibility of ASCT.

Blinatumomab is a bispecific T-cell engager that recruits T-cell on CD19 positive blast cells and induces anti-leukemic cytotoxicity. In a phase 3 trial in relapse/refractory Philadelphia-negative (Ph-) ALL, 43% of patients achieved a CR or CR with partial hematological recovery (CRh), with the majority of responses occurring within the first cycle. In patients with positive MRD (MRD+) BCP-ALL, blinatumomab resulted in complete MRD response in 78% of patients after one cycle.

Between 2012 and 2016, blinatumomab was available in France for R/R and MRD+ ALL adult patients through the French Compassionate Use Program. About 92 adult ALL were treated at different stages of the disease in 27 centers.