General Information

Blincyto (blinatumomab) is an immunotherapy. It engages the body’s T-cells, a type of white blood cell or lymphocyte, to destroy leukemia cells. The drug acts as a connector between a protein called CD19, which is found on the surface of most B-cell lymphoblasts, and CD3, a protein on T-cell lymphocytes.

Blincyto is specifically indicated for the treatment of adults and children with:

• CD19-positive B-cell precursor acute lymphoblastic leukemia (ALL) in first or second complete remission with minimal residual disease (MRD) greater than or equal to 0.1%. This indication is approved under accelerated approval based on MRD response rate and hematological relapse-free survival. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.
• Relapsed or refractory CD19-positive B-cell precursor acute lymphoblastic leukemia

Blincyto is supplied as a solution for intravenous infusion. Hospitalization is recommended for the first 9 days of the first cycle and the first 2 days of the second cycle. For all subsequent cycle starts and reinitiation (eg, if treatment is interrupted for 4 or more hours), supervision by a healthcare professional or hospitalization is recommended. Do not flush the Blincyto infusion line, especially when changing infusion bags. Flushing when changing bags or at completion of infusion can result in excess dosage and complications. The recommended dosing schedule is as follows:

A single cycle of treatment of Blincyto consists of 4 weeks of continuous intravenous infusion followed by a 2-week treatment-free interval.
• For patients at least 45 kg in weight:
- In Cycle 1, administer Blincyto at 9 mcg/day on Days 1–7 and at 28 mcg/day on Days 8–28.
- For subsequent cycles, administer Blincyto at 28 mcg/day on Days 1–28.
• Allow for at least 2 weeks treatment-free between cycles of Blincyto.
• A treatment course consists of up to 2 cycles of Blincyto for induction followed by 3 additional cycles for consolidation treatment (up to a total of 5 cycles).  

Mechanism of Action

Blincyto (blinatumomab)  is a bispecific CD19-directed CD3 T-cell engager that binds to CD19 expressed on the surface of cells of B-lineage origin and CD3 expressed on the surface of T cells. It activates endogenous T cells by connecting CD3 in the T-cell receptor (TCR) complex with CD19 on benign and malignant B cells. Blinatumomab mediates the formation of a synapse between the T cell and the tumor cell, upregulation of cell adhesion molecules, production of cytolytic proteins, release of inflammatory cytokines, and proliferation of T cells, which result in redirected lysis of CD19+ cells. 

Side Effects

Adverse effects associated with the use of Blincyto may include, but are not limited to, the following:

• pyrexia
• headache
• peripheral edema
• febrile neutropenia
• nausea
• hypokalemia
• tremor
• rash
• constipation

In addition, Cytokine Release Syndrome (CRS) and neurological toxicities, both of which may be severe, life-threatening, or fatal, occurred in patients receiving Blincyto. Interrupt or discontinue Blincyto as recommended. 

Clinical Trial Results

The FDA approval of Blincyto was granted under accelerated approval conditions. Continued approval for this indication may be contingent upon verification of clinical benefit in subsequent trials. Accelerated approval was based on an open-label, multicenter, single-arm study in adults with Philadelphia chromosome-negative relapsed or refractory B precursor ALL. Blincyto was administered as a continuous intravenous infusion. In the first cycle, the initial dose was 9 mcg/day for week 1, then 28 mcg/day for the remaining 3 weeks. The target dose of 28 mcg/day was administered in cycle 2 and subsequent cycles starting on day 1 of each cycle. Dose adjustment was possible in case of adverse events. The treated population included 185 patients who received at least 1 infusion of Blincyto; the median number of treatment cycles was 2. Patients who responded to Blincyto but later relapsed had the option to be retreated with Blincyto. Among treated patients, the median age was 39 years (range: 18 to 79 years), 63 out of 185 (34.1%) had undergone HSCT prior to receiving Blincyto, and 32 out of 185 (17.3%) had received more than 2 prior salvage therapies. The primary endpoint was the complete remission/complete remission with partial hematological recovery (CR/CRh) rate within 2 cycles of treatment with Blincyto. Seventy-seven out of 185 (41.6%) evaluable patients achieved CR/CRh within the first 2 treatment cycles, with the majority of responses (81%, 62 out of 77) occurring within cycle 1 of treatment. The HSCT rate among those who achieved CR/CRh was 39% (30 out of 77).