The European Commission has approved blinatumomab for the treatment of pediatric patients with Philadelphia chromosome–negative, CD19-positive B-cell precursor acute lymphoblastic leukemia that is refractory or in relapse after receiving at least 2 prior therapies or in relapse after receiving prior allogeneic hematopoietic stem cell transplantation.
David M. Reese, MD
The European Commission (EC) has approved blinatumomab (Blincyto) for the treatment of pediatric patients with Philadelphia chromosome—negative (Ph-), CD19-positive B-cell precursor acute lymphoblastic leukemia (ALL) that is refractory or in relapse after receiving at least 2 prior therapies or in relapse after receiving prior allogeneic hematopoietic stem cell transplantation (HSCT).1
The approval of the anti-CD19 immunotherapy was based on data from a single-arm phase I/II trial, known as Study 205, which met its primary phase II endpoint of complete remission (CR) within the first 2 cycles of blinatumomab.
“Historically, children with relapsed or refractory ALL have had limited pharmacologic options beyond chemotherapy, resulting in poor outcomes,” David M. Reese, MD, executive vice president of Research and Development at Amgen, the manufacturer of blinatumomab, said in a statement. "This approval for Blincyto provides physicians across Europe with an important new immunotherapy option for these young, heavily pretreated patients, delivering on Amgen's commitment to making a difference in the lives of cancer patients."
The multicenter, dose-finding, efficacy Study 205 trial accrued patients aged <18 years with Ph- B-cell precursor ALL who were refractory, had relapsed at least twice, or relapsed after an allogeneic HSCT.
Patients received blinatumomab as a continuous infusion at 5 μg/m2/day on days 1 to 7 and 15 μg/m2/day on days 8 to 28 for cycle 1, followed by 2 weeks off, and 15 μg/m2/day on days 1 to 28, followed by 2 weeks off for subsequent cycles. Overall, the mean number of treatment cycles was 1.5. Individuals who relapsed after an initial response to blinatumomab could choose to be retreated.
Seventy patients received the recommended treatment dose. Among these patients, the median age was 8 (range, 7 months to 17 years), 57.1% (n = 40) had received allogeneic HSCT before blinatumomab, and 55.7% (n = 39) had refractory disease.
Overall, 20 (28.6%) patients had a CR or CR with partial hematologic recovery within 2 treatment cycles. Eighty-five percent (n = 17) of the responses occurred within the first cycle.1
Based on the same study, the US FDA approved blinatumomab in September 2016 for use in this setting. At the time of the FDA approval, it was reported that the most common grade ≥3 adverse events (AEs) among the 70 patients receiving the recommended dose were anemia, thrombocytopenia, febrile neutropenia, hypokalemia, and neutropenia. Serious AEs were reported to be comparable to those previously reported for blinatumomab in adult patients.
In June 2018, the EC granted blinatumomab full marketing authorization for the treatment of adult patients with Ph- relapsed/refractory B-cell precursor ALL. The EC had previously awarded the agent a conditional marketing authorization in this setting in 2015 that was contingent on data from a confirmatory trial.
The action was based on survival data from the phase III TOWER study, in which the median overall survival (OS) with blinatumomab was 7.7 months versus 4 months with standard chemotherapy for patients with Ph-negative relapsed/refractory B-cell precursor ALL. Treatment with blinatumomab reduced the risk of death by 29% versus standard chemotherapy (HR, 0.71; 95% CI, 0.55-0.93; P = .012).2,3 Among patients receiving blinatumomab as their first salvage treatment, the median OS was 11.1 versus 5.3 months, respectively (HR, 0.6; 95% CI, 0.39-0.91).
Blinatumomab is a recombinant, single-chain monoclonal antibody that possesses antigen-recognition sites for CD3 and CD19. The CD3 complex consists of T cell surface glycoproteins, while CD19 is a tumor-associated antigen. The combination of these recognition sites into 1 therapy is thought to promote cytotoxic T lymphocyte and helper T lymphocyte activity against CD19-expressing B lymphocytes.