About 40% of acute lymphocytic leukemias (ALLs) occur in adults, but those cases are responsible for 80% of ALL’s death rate. 

The high mortality is attributed to 33% of standard-risk patients and 66% of high-risk patients experiencing disease relapse. When ALL fails multiple therapies, only 20%–30% of patients can expect to achieve complete remission (CR) and be eligible for curative treatment with allogeneic stem cell transplantation.

Blinatumomab is a single-agent therapy approved by the U.S. Food and Drug Administration (FDA) in 2014 for relapsed or refractory Philadelphia chromosome-negative B-cell ALL. The drug targets CD19, a surface antigen expressed in B-cell development and in more than 95% of B-precursor ALL blasts. It also targets CD3, a T-cell coreceptor. It simultaneously binds CD3-positive cytotoxic T cells and CD19-positive B cells, causing the T cells to induce lysis of the normal and malignant B cells.

Two studies have shown the blinatumomab is effective in inducing remissions in refractory B-cell ALL. The first, a phase II study of 36 patients, administered blinatumomab as a four-week continuous infusion followed by two weeks without treatment. A total of 69% of patients received CR or complete remission with partial recovery of peripheral blood counts (CRh).

The follow-up phase II study led to the drug’s FDA approval and treated 189 adult patients from 23 European and 14 U.S. cancer centers. It used the same treatment regimen as the original study with a dose of 9 mcg per day for one week followed by 28 mcg for three weeks. After the second cycle, 43% of patients had achieved CR or CRh. Forty percent of those patients went on to receive the curative allogeneic stem cell transplant.

The most common adverse events were pyrexia, neurologic symptoms, headache, febrile neutropenia, peripheral edema, nausea, hypokalemia, constipation, and anemia. Most were grade 1 or 2 and occurred during the first treatment cycle. They were managed with dexamethasone without interrupting treatment. Cytokine-release syndrome was an infrequent but life-threatening toxicity occurring in 2%–6% of patients; the incidence was lowered when patients were pretreated with dexamethasone.

Blinatumomab is currently being studied for other indications, including Philadelphia chromosome-positive relapsed or refractory adult ALL, recurrent ALL in children and adolescents, older adults with newly diagnosed ALL, adults with refractory diffuse large B-cell lymphoma, and in combination with other chemotherapy agents as first-line treatment for newly diagnosed ALL in adults.