How is this drug name pronounced?
What cancer(s) does this drug treat?
Blincyto is approved for:
B-precursor Acute Lymphoblastic Leukaemia (ALL)
- Adults and children with B-precursor Acute Lymphoblastic Leukaemia (B-ALL) who had been treated with chemotherapy, targeted therapy or allogeneic stem cell transplantation, but the cancer either did not respond to treatment (refractory) or has since returned (relapsed). The cancer cells must express the CD19 molecule on their surface.
B-precursor Acute Lymphoblastic Leukaemia (ALL) which is MRD-positive
- Patients with B-precursor Acute Lymphoblastic Leukaemia (B-ALL) for whom chemotherapy was mostly successful, but a small number of cancer cells still remain (a condition known as Minimal Residual Disease [MRD]). These cells may put the patient at an increased risk of relapse, and Blincyto can be prescribed to eliminate all remaining traces of the cancer.
Limitations of use
Age: The safety and efficacy of Blincyto have not been established in pediatric patients less than 1 year of age.
Weight: Use of Blincyto containing preservative is not recommended for patients weighing less than 22 kg. Benzyl alcohol is used as a preservative in Blincyto and can often cause adverse reactions in patients below this weight limit.
Pregnancy/breastfeeding: Blincyto is not recommended for use in women who are pregnant or breastfeeding. Appropriate contraceptive measures should be used by women of child-bearing potential while receiving Blincyto, and for two days after the last dose.
What type of immunotherapy is this?
- Bispecific antibody therapy
How does this drug work?
- CD19 receptor on B cells
- CD3 receptor on T cells
Blincyto is a “bispecific antibody”. Antibodies are molecules which can bind to a particular target molecule. Bispecific antibodies are artificially made in the laboratory and can bind to two different targets at the same time. Blincyto binds to:
- a molecule called CD19 on the surface of a leukemic B cell. CD19 is found on the surface of all human B cells, where it is almost always present due to its importance to their normal function, however it is also present on the surface of B-precursor ALL cells.
- a molecule called CD3 on the surface of a T cell – the primary immune cell involved in killing cancer cells. CD3 is part of the T cell receptor, which is critical to the function of the T cell and is involved in stimulating the T cell to become active.
Because Blincyto can bind to one molecule on leukemic B cells and one on T cells at the same time, it acts as a bridge and keeps the T cell in close contact with the leukemic B cell. By binding CD3 on the T cell, Blincyto also stimulates the T cell to become activated and kill nearby cells. Bispecific antibodies that direct T cells to kill cancer cells by binding to both cells at the same time are known as bispecific T cell engagers (BiTEs).
How is the drug given to the patient?
Blincyto is administered via a tube into a vein (intravenous infusion, or I.V.) continuously for 28 days, followed by a break of 14 days. The combined period of the 28-day treatment and the 14-day break is one “cycle”. Blincyto is administered across multiple treatment cycles.
One hour prior to the first dose of Blincyto in each cycle, adult patients are pre-medicated with an anti-inflammatory drug (prednisone or equivalent). Pediatric patients are pre-medicated with the anti-inflammatory drug dexamethasone prior to the first dose of Blincyto in the first cycle, and when restarting an infusion after any interruptions of 4 or more hours in the first cycle.
Hospitalization is recommended for the first 9 days of the first cycle for patients with relapsed/refractory B-ALL (who had been treated with chemotherapy, but it either did not work or stopped working) and the first 3 days of the first treatment cycle for patients with minimal residual disease B-ALL. For subsequent cycles, fewer hospitalization days are required. Hospitalization or supervision by a healthcare professional is also recommended for all subsequent cycle starts, and when restarting an infusion after any interruptions.
The first treatment cycle (for patients with minimal residual disease B-ALL) or the first two cycles (for patients with relapsed/refractory B-ALL) are intended to drastically reduce or eliminate leukemic cells and decrease cancer-associated symptoms. These are called “induction cycles”. After the induction cycle(s), up to three more cycles are administered in order to further reduce the leukemic cells and prevent the disease from returning after discontinuing Blincyto. These are called “consolidation cycles”. Patients with relapsed/refractory B-ALL can then receive up to 4 additional cycles of Blincyto with a break of 56 days (“continued therapy”).
What are the observed clinical results?
It is important to keep in mind that each patient’s outcome is individual and may be different from the results found in the clinical studies. In addition, immunotherapy can sometimes take several months to yield an observable treatment response.
Philadelphia chromosome-negative relapsed or refractory B-precursor Acute Lymphoblastic Leukaemia (B-ALL)
In a clinical trial of 405 adult patients with Philadelphia chromosome-negative relapsed or refractory B-ALL (who had been treated with chemotherapy or allogeneic stem cell transplantation, but it either did not work or stopped working), patients treated with Blincyto were alive for a median of 8 months, while patients treated with standard-of-care chemotherapy were alive for a median of 4 months. 42% of patients treated with Blincyto had their cancer completely disappear (complete remission), compared to 20% of patients achieving complete remission with a physician’s choice of any of 4 standard-of-care chemotherapies.
In a clinical trial of 45 adult patients with Philadelphia chromosome-positive B-ALL who had been previously treated with imatinib (Gleevec) and other targeted therapies, but for whom treatment either did not work, stopped working, or was stopped because it caused severe side effects for the patient, 36% of patients treated with Blincyto had their cancer completely disappear (complete remission). The remission lasted for a median of 7 months.
In a trial of 70 pediatric patients (under 18 years of age) with Philadelphia chromosome-negative B-ALL that had returned or had not responded to previous treatments, 33% of patients treated with Blincyto had their cancer completely disappear (complete remission). The remission lasted for a median of 6 months.
MRD-positive B-precursor Acute Lymphoblastic Leukaemia (B-ALL)
In a clinical trial of 86 patients with minimal residual disease (MRD) B-ALL, leukemia cells could no longer be detected in 81% of the patients after one cycle of Blincyto.
What are the potential side effects?
Blincyto targets the CD19 molecule, which, while present on leukemic B cells, is also present on normal B cells. As a result, Blincyto can kill normal B cells, increasing the risk of serious infections. Other common side effects of Blincyto include fever, headache, low white blood cell count, low red blood cell count, low platelet count, abnormal liver blood tests, inflammation of the pancreas, and reactions related to the infusion. Some side effects, such as cytokine release syndrome (CRS) or neurological toxicities, can become serious or life-threatening. Patients and caregivers receive careful instructions to monitor for signs and symptoms related to CRS and neurological toxicities. Both conditions are managed by the health care provider.
Cytokine release syndrome (CRS)
CRS is caused by a widespread release of molecules called cytokines, which can cause inflammation and can affect the function of various organs. Cytokines may be released by the T cells to which Blincyto binds, or by other immune cells in the patient’s body. Signs and symptoms of CRS include fever, headache, nausea, low blood pressure, and weakness. CRS typically occurs 2 days after the start of Blincyto infusion. A healthcare provider should be immediately notified if symptoms occur.
Some of the cytokines released during CRS can result in disruption of the blood-brain barrier, leading to the development of neurological toxicities. Symptoms of neurological toxicities include headache, tremors, seizures, loss of consciousness, confusion, difficulty with speech, and loss of balance. Neurological toxicities typically occur within the first two weeks of treatment with Blincyto.
For a more complete list of possible side effects, see the full prescribing information.
FDA and EMA