Micromet: Study Demonstrates Micromet's Blinatumomab Produces High Single-Agent Activity in Patients with Relapsed Acute Lymphoblastic Leukemia

Data to be presented tomorrow at the 16th Annual Meeting of the European Hematology Association in London, UK, show that Micromet's blinatumomab produced a high complete remission rate in adult patients with acute lymphoblastic leukemia who had relapsed following treatment with standard therapy.1 Blinatumomab is the most advanced of a new class of agents called BiTE® antibodies, designed to harness the body's T cells to kill cancer cells. Interim results from this phase 2 single-arm trial showed that 75% of patients (9 of 12) achieved a complete remission or CR with partial recovery of blood counts following treatment with blinatumomab. All nine responding patients achieved a complete molecular response, or had no evidence of leukemic cells in their bone marrow, a key prognostic factor for patient survival. Notably, four patients with genetic abnormalities typically associated with poorer outcomes all achieved a CR or CRh*. “Relapsed/refractory acute lymphoblastic leukemia is a difficult to treat disease that has seen no meaningful improvement in decades,” said Professor Max Topp, Department of Internal Medicine II, University of Wuerzburg and the chair of the study. “To date blinatumomab has shown an impressive and unprecedented level of efficacy in a patient population with limited therapeutic options." The most common clinical adverse events were fever, peripheral edema and fatigue. Treatment of two of the twelve patients was interrupted due to fully reversible and manageable CNS events. In one patient, cytokine release syndrome was observed, which was mitigated in subsequent patients through dose modification and pre-treatment with concomitant medication. No additional cytokine release syndrome was observed. “These results are particularly striking relative to the fact that the majority of enrolled patients had characteristics typically associated with a dismal outlook,” said Professor Topp. Current treatment for Philadelphia negative relapsed/refractory ALL consists of combinations of toxic chemotherapy drugs that in the majority of cases fail to drive the disease into remission. In more than 30 years, no new drug has been approved for use in this setting, leaving physicians with few options to improve long-term patient outcomes other than variations in the dose and schedule of old drugs with limited efficacy. With current approaches, complete remission rates range from 17-45%.2-6 Standard chemotherapy is associated with a mortality rate of up to 23%.7 The average five-year survival rate for adult ALL patients after first relapse is 7%.5 Study design This study is designed to evaluate the efficacy, safety and tolerability of blinatumomab in up to 25 adult patients with B-precursor ALL who relapsed after at least induction and consolidation treatment or who have refractory disease. Patients receive blinatumomab as a continuous infusion for 28 days followed by a treatment free interval of two weeks. Patients who achieve a CR/CRh* within the first two treatment cycles can receive consolidation with either three additional cycles of blinatumomab or allogeneic HSCT. The primary endpoint of the study is the rate of CR/CRh*. Secondary endpoints include molecular response rate, duration of response and overall survival. Enrollment in this study is currently on-going.