CHICAGO – The novel antibody blinatumomab continues to induce high complete remission rates in adults with relapsed or refractory B-precursor acute lymphoblastic leukemia.
In a phase II study with a dose-finding phase, 26 of 36 patients treated at various dose levels had a complete response (CR) or a complete response with partial hematologic recovery (CRh) within two treatment cycles, Dr. Max S. Topp reported at the annual meeting of the American Society of Clinical Oncology. Of 23 patients treated at the optimal dose, 17 had a CR or CRh, he said.
Dr. Max Topp
All but two of the patients with responses to the drug also had a molecular remission, he noted, and 13 patients went on to receive an allogeneic stem cell transplant after achieving a CR or CRh.
"We reached a very high rate of hematological and molecular remission in patients with blinatumomab," said Dr. Topp of the University of Würzburg (Germany).
The median duration of complete hematologic remission among all patients treated in the dose-finding phase was 8.9 months (median follow-up, 4.5 months). Median overall survival among patients treated at all dose levels was 9 months (median follow-up, 10.7 months).
Blinatumomab is a bispecific T-cell engager (BiTE) antibody designed to direct cytotoxic T cells to cancer cells expressing the CD19 receptor. It showed good activity in a phase I clinical trial in patients with relapsed non-Hodgkin’s lymphoma, as well as in a study of patients with B-lineage acute lymphoblastic leukemia (ALL) who were positive for minimal residual disease (J. Clin. Oncol. 2011;29:2493-8). Dr. Topp reported earlier results of the current MT103-206 study at the 2011 annual meeting of the American Society of Hematology.
The current trial was an open-label, multicenter phase II study of blinatumomab in patients with relapsed/refractory B-precursor ALL, or Philadelphia chromosome–positive ALL, who were ineligible for tyrosine kinase inhibitors or who were in relapse following an allogeneic stem cell transplant.
The trial had a dose-finding run-in phase with four patient cohorts. Dr. Topp provided updated outcomes data on cohorts 2a and 3 (the extension phase), in which patients received the selected dose schedule: an initial dose of 5 mcg/m2 IV daily for the first week of cycle 1, followed by 15 mcg/m2 per day for weeks 2-4 of every 4-week cycle, and every subsequent cycle. Patients had 2 weeks off between each cycle.
Patients who had a CR or CRh in the first two treatment cycles underwent consolidation with three additional cycles of blinatumomab and allogeneic stem cell transplant.
Medically important safety events to date include the cytokine release syndrome in three patients, two of whom had a high tumor burden with no cytoreductive prephase; and these patients required temporary treatment interruption. The third patient had a milder form of the syndrome and was managed with supportive medication, with no discontinuation of blinatumomab.
Six patients had central nervous system adverse events – three seizures and three cases of encephalopathy – that were reversible with treatment interruption. All six were eventually continued on the 5-mg/m2 dose, but two had recurrence and permanently stopped treatment. One patient stopped because of a fungal infection that proved to be fatal.
Pyrexia, headache, tremor, and fatigue were the most common treatment-emergent adverse events, but there were only four grade 3 or higher reactions, including one increase in cytokine release syndrome. Most of the events occurred at the start of the first cycle.
The invited discussant, Dr. Bruno Medeiros of Stanford (Calif.) University, commented that blinatumomab appears to have good single-agent activity in relapsed or refractory ALL and is safe before allogeneic transplant. This agent, and another novel antibody against acute lymphocytic leukemia, inotuzumab, may also be effective when combined with chemotherapy or as single agents in first-line therapy, he said.
A global phase II study of blinatumomab in patients with relapsed or refractory ALL is underway.
The study was funded by Micromet, which has been acquired by Amgen. Dr. Topp disclosed having a consultant or advisory role and receiving other remuneration from Micromet. Dr. Medeiros disclosed ties with Millennium, Celgene, and Novartis.