Anti-CD19 Bispecific T Cell Engager Blinatumomab Shows Activity in Relapsed/Refractory B-Precursor ALL
In a phase II study reported in the Journal of Clinical Oncology, Topp et al found that the bispecific T-cell engager (BiTE) antibody blinatumomab produced a high response rate in patients with relapsed or refractory B-precursor acute lymphoblastic leukemia (ALL). BiTEs induce a transient cytolytic synapse between cytotoxic T cells and target cancer cells, allowing the T cells to transfer toxic content into the latter.
Study Details
In the study, 36 patients (median age = 32 years, range = 18–77 years) received blinatumomab in cycles of 4-week continuous infusion followed by a 2-week treatment-free interval in dose-finding and extension stages. Daily doses consisted of 15 µg/m2, 5 µg/m2 increased to 15 µg/m2, and 5 µg/m2 increased to 15 µg/m2 and then to 30 µg/m2. Blinatumomab was administered in the hospital during the first week of the first cycle and during the first 2 days of each subsequent cycle, and on an outpatient basis thereafter.
Responses
Complete remission or complete remission with partial hematologic recovery occurred in 25 patients (69%), with minimal residual disease response observed in 88% of responders. Median overall survival was 9.8 months (95% confidence interval [CI] = 8.5–14.9 months), and median recurrence-free survival was 7.6 months (95% CI = 4.5–9.5 months). Of responders, 13 (52%) underwent hematopoietic stem cell transplantation after achieving complete remission or complete remission with partial hematologic recovery..
Toxicity
The most common adverse events of any grade were pyrexia (81%), fatigue (50%), headache (47%), tremor (36%), and leukopenia (19%). Among 23 patients receiving the optimal dose of 5 to 15 µg, the most common grade ≥ 3 adverse events (total 65% of patients) were thrombocytopenia, tremor, and hypertension (9% each).
Serious adverse events occurred in 76%, including infection (33%) and nervous system and psychiatric disorders (22%). Two patients had grade 4 cytokine release syndrome, with treatment being interrupted in one and discontinued in one. Treatment was interrupted in six patients with nervous system or psychiatric disorders.
The investigators concluded: “The data support further investigation of blinatumomab for the treatment of adult patients with relapsed or refractory ALL in a larger confirmatory study.”
Max S. Topp, MD, of Universitätsklinikum Würzburg, is the corresponding author for the Journal of Clinical Oncology article.
The study was supported by Amgen. For full disclosures of the study authors, visit jco.ascopubs.org.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
