(CHICAGO, IL) — Adult patients with relapsed/refractory B-precursor acute lymphoblastic leukemia (ALL) treated with the bispecific T-cell engaging (BiTE) antibody blinatumomab had a 72% response rate, according to results of a dose-ranging Phase 2 trial presented at the 2012 American Society of Clinical Oncology Annual Meeting.
Blinatumomab directs cytotoxic T-cells to CD19 expressing target cells. In this efficacy and safety study, three dose levels were explored that resulted in a final dose of 5µg/m²/day in Week 1 and 15µg/m²/day for the remaining treatment period, explained Prof. Dr. Max S. Topp, of Wuerzburg University Hospital, Wuerzburg, Germany.
The primary endpoint was rate of hematological complete remission (CR) or CR with partial hematological recovery (CR/CRh) within two cycles of treatment with blinatumomab, which is administered by continuous IV infusion for 28 days followed by a 14-day treatment-free interval. Patients who responded were eligible to receive 3 additional cycles of treatment or proceed to bone-marrow transplantation.
The study enrolled 36 patients; 26 were evaluable and 72% had attained a CR/CRh and a minimal residual disease (MRD) response (MRD level <10-4) within the first 2 cycles. All but 2 responders achieved molecular remission, and there was a high remission rate in all patient subgroups. A total of 13 patients received an allogeneic stem-cell transplant after achieving CR/CRh.
Duration of hematologic complete response was 8.9 months in 25 patients and median overall survival was 9.0 months at an overall median follow-up of 10.7 months. The most common treatment emergent adverse events in 23 patients, all grades, were pyrexia (70%), headache (39%), and tremor (30%); grade ≥3 pyrexia occurred in 4% of patients, tremor in 9%, and CRP increase in 4%. Two patients with a high tumor burden and no cytoreductive pre-phase required temporary treatment discontinuation or interruption, and one patient with a milder form of cytokine release syndrome was managed with supportive medication; no interruption of blinatumomab was required.
Fully reversible CNS adverse events leading to treatment interruptions were observed in 6 patients; events included 3 patients with seizures and 3 with encephalopathy; however, resolution was prompt following infusion interruption and all 6 continued at the 5µg/m²/day dose. Two patients subsequently had a recurrent event and permanently stopped treatment. One patient stopped treatment due to a fungal infection that eventually led to death.
“The data support further investigation of blinatumomab in adult patients with relapsed/refractory ALL,” said Dr. Topp. He added that a global Phase 2 study in this setting has been initiated.