Early results of blinatumomab in children with relapsed ALL

This study examined the safety and effects of blinatumomab (Blincyto) in children with relapsed acute lymphoblastic leukemia (ALL). Researchers concluded that blinatumomab can achieve complete remission in some children with unfavorable ALL.

ALL is a cancer of the blood and bone marrow. Chemotherapy is usually the first-line treatment of ALL. In cases of a relapse (return of the disease) of ALL, alternative treatment options are usually explored. This is because many patients develop a resistance to standard chemotherapy over time. Blinatumomab is a newly developed type of targeted therapy called a monoclonal antibody. Monoclonal antibodies are made in the laboratory from a single type of immune system cell. These antibodies can identify substances on cancer cells or normal substances in the body involved in cancer growth. The effectiveness of blinatumomab for children with relapsed ALL is still being investigated.

The aim of this study was to examine the effectiveness of blinatumomab for children with relapsed ALL.

Children with high-risk ALL no longer responding to standard chemotherapy, in their second relapse, and/or in relapse after a stem cell transplant were included in this study. All patients were treated with blinatumomab in 6-week treatment cycles. 49 patients were included in the first phase of the study that examined different dosages of blinatumomab. 44 patients were included in the second phase that examined remission rates after 2 cycles of blinatumomab. Patients were followed for up to 2 years.

4 patients were not able to complete the increases in blinatumomab dosage in phase 1 due to side effects. 2 of these patients died due to treatment-related complications. One patient died from heart failure and one patient died from respiratory failure. 3 patients showed signs of severe cytokine-release syndrome. This refers to a specific reaction to some immunotherapies. The maximum-tolerated daily dosage was 15 µg/m2. On the basis of the first phase of the study, the recommended blinatumomab dosage for children with relapsed ALL was 5 µg/m2 per day for the first 7 days followed by 15 µg/m2 per day thereafter.

70 patients received the recommended blinatumomab dosage over the two phases of the study. 27 patients (39%) achieved a complete remission (CR; no sign of disease) within the first 2 treatment cycles. Of these, 74% achieved CR within the first cycle. 52% of patients who achieved CR reached complete minimal residual disease response (no measurable leukemia cancer cells after treatment).

Of the 27 responders, 4 patients (14.8%) were still in CR at 2 years. 2 patients had relapsed but were still alive. 3 patients had withdrawn from the study. 3 patients died while in remission after undergoing a stem cell transplant. 15 patients had relapsed and died. Of the 43 non-responders, 8 patients (18.6%) were still alive at 2 years.

At the recommended dose, blinatumomab was associated with fever (80% of patients), low hemoglobin levels (41%), nausea (33%), and headache (30%). Serious side effects included very low hemoglobin levels (36% of patients), low platelet counts (21%), and low potassium levels (17%). 2 patients interrupted treatment after experiencing a mild seizure.

Researchers concluded that blinatumomab can achieve complete remission in some children with unfavorable ALL. 

More studies are needed to confirm these preliminary results.