By Mary Ellen Schneider
Blinatumomab monotherapy before allogeneic hematopoietic stem cell transplant could become a new standard of care for children with high-risk, first-relapse B-cell precursor acute lymphoblastic leukemia (BCP-ALL), findings presented at the annual meeting of the American Society of Hematology suggest.
The phase 3, randomized controlled trial compared the bispecific T-cell engager blinatumomab to high-risk consolidation chemotherapy as pretransplant consolidation therapy for children with high-risk, first-relapse BCP-ALL (Abstract 268). Blinatumomab monotherapy achieved significantly better event-free survival, causing the trial’s data monitoring committee to recommend early termination of enrollment due to benefit.
“This data clearly indicated that monotherapy with blinatumomab constitutes a new standard of care as pretransplant treatment in children with high-risk, first relapse of B-cell precursor ALL,” said Franco Locatelli, MD, PhD, of the IRCCS Ospedale Pediatrico Bambino Gesu and Sapienza, University of Rome, Italy, who presented the study results.
The study included children under age 18 years who had high-risk first relapse BCP-ALL, M1 or M2 marrow at randomization, no current central nervous system involvement, and no clinically relevant central nervous system pathology. Patients were stratified by age, bone marrow status, and minimal residual disease status. Patients were allowed to be treated with different chemotherapy protocols during the trial. Patients received induction therapy, followed by two courses of chemotherapy before being randomized to receive either a third course of chemotherapy or one cycle of blinatumomab monotherapy at a dose of 15 μg/m2/day.
In total, 108 patients were randomized to either blinatumomab or chemotherapy consolidation. Events were reported for 32% of patients receiving blinatumomab and 57% of patients receiving chemotherapy (Hazard Ratio [HR] 0.33; 95% CI 0.18-0.61). The median event-free survival was not reached in the blinatumomab arm and was 7.4 months in the chemotherapy arm.
Patients who received blinatumomab also had a longer overall survival (HR 0.43) and a lower incidence of relapse. Researchers also observed superior minimal residual disease remission in the blinatumomab arm at 90%, compared with 54% with chemotherapy. This was a treatment difference of 36% (95% CI, 19-52).
Blinatumomab also appears to have fewer and less severe toxicities, Dr. Locatelli said. Patients receiving blinatumomab had a lower incidence of grade 3 or greater neutropenia, anemia, leukopenia, cytopenia, aplasia, and febrile neutropenia. Grade 3 and 4 neurologic events were similar between the two arms. No patients in the study experienced grade 3 or higher cytokine release syndrome, which Dr. Locatelli said was likely because of the low tumor burden at the time of randomization.