Blinatumomab Received Accelerated FDA Approval for Precursor B-Cell ALL Treatment

On 29 March 2018, the United States Food and Drug Administration, FDA, for precursor B-cell acute lymphoblastic leukemia (ALL) in first or second complete remission with minimal residual disease (MRD), 0,1% or greater, in adult and pediatric patients, granted blinatumomab (brand name Blincyto) accelerated approval for treatment.

Approval was based on BLAST, an open-label, multicenter, single-arm study of patients aged at least 18 who had received at least 3 chemotherapy treatments from standard ALL therapies, were in complete hematological remission (<5% blasts, absolute neutrophil count >1Gi/L, platelets >100Gi/L), and, using a test with minimum sensitivity of 0.01%, had MRD equal to or greater than 0.1%; 86 patients were included. Blinatumomab was given intravenously at a fixed dose of 15 mcg/m2/day in all cycles (equivalent to the recommended 28 mcg/day dose). Patients received up to 4 cycles. Following blinatumomab, among patients in first complete remission, 61 patients (74%) included 45 who underwent transplantation; among those in second complete remission, 25 included 14 (56%) undergoing transplantation while in ongoing hematological complete remission, allogeneic hematopoietic stem cell transplantation was performed.

Efficacy was based on achieving undetectable minimal residual disease (MRD) within one cycle of blinatumomab and the hematological relapse-free survival (RFS) rate. The test used to assess MRD response, for 6 patients, had sensitivity of 0.01%, and for 80 patients, sensitivity equal to or below 0.005%. Overall, undetectable MRD was achieved in 52 patients in first complete remission and 18 in second complete remission. In the majority of patients who underwent transplantation, median estimated hematological RFS was 35.2 months for those in first complete remission and 12.3 months for those in second complete remission.

In at least 20% of patients with MRD-positive precursor B-cell ALL, the most common blinatumomab side effects were fever, infusion-related reactions, headache, infections, palpitations and chills. Serious adverse effects were reported in 61%. In at least 2%, the most common adverse effects included fever, chills, encephalopathy (brain disease), speech impairment, low white blood cells, overdose, device-related infection, seizures and staphylococcal infection. In 64%, grade three or higher adverse effects were also reported. Treatment discontinuation due to adverse effects occurred in 17%, with neurological events the most commonly reported reason. Within 30 days of completing blinatumomab treatment, two fatal adverse effects (atypical pneumonia and subdural hemorrhage) were reported.