ORLANDO – Minimal residual response (MRD) induced by blinatumomab montherapy was associated with longer overall survival, relapse-free survival, and duration of response compared with not achieving an MRD complete response in patients with MRD+ acute lymphoblastic leukemia (ALL), a study presented at the American Society of Hematology annual meeting has shown.1
“This is a proof-of-principle study with a new compound in an MRD-positive population with an MRD-based endpoint,” lead investigator Nicola Gökbuget, MD, of the Goethe University Department of Medicine II in Frankfurt, Germany, said during her presentation.
For the study, researchers enrolled 116 patients with B-cell precursor ALL with hematologic complete remission and MRD ≥ 10-3 after 3 or more intensive chemotherapy treatments. All patients received blinatumomab 15 μg/m2/day administered by continuous intravenous infusion for 4 weeks, followed by 2 weeks off, in a 6-week cycle. Patients with MRD positivity after the first cycle received up to 3 additional cycles or underwent hematopoietic stem cell transplantation (HSCT), while patients with hematologic relapse discontinued treatment.
“Blinatumomab induced a high complete MRD response rate of 80%,” Dr Gökbuget noted. “Sixty-seven percent of the patients were able to receive stem cell transplantation in continuous remission after blinatumomab.”
Blinatumomab may also contribute to prolonged relapse-free survival and overall survival in patients with MRD-positive ALL and MRD response was associated with improved overall survival, relapse-free survival, and duration of response. Furthermore, patients treated in first remission had improved relapse-free survival and duration of response compared with those treated in subsequent remission.
In regard to safety, the most clinically relevant adverse events were neurologic events, including tremor, aphasia, dizziness, ataxia, paresthesia, and encephalopathy.
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“Among patients who experienced neurologic events on study, most had a worst event of grade 2 or higher. Twelve patients interrupted or discontinued treatment due to grade 3 or higher neurologic events,” Dr Gökbuget explained.
Blinatumomab is a bispecific T cell engager (BiTE) antibody construct that redirects CD3+ T cells to CD19+ target cells, leading to serial lysis of CD19+ B cells. It is approved by the U.S. Food and Drug Administration for the treatment of patients with Philadelphia chromosome-negative relapsed or refractory B-cell precursor ALL.
- Gökbuget N, Dombret H, Bonifacio M, et al. Long-term outcomes after blinatumomab treatment: Follow-up of a phase 2 study in patients (Pts) with minimal residual disease (MRD) positive B-cell precursor acute lymphoblastic leukemia (ALL). Oral presentation at: 57th American Society of Hematology (ASH) Annual Meeting & Exposition; December 5-8, 2015; Orlando, FL.