= Additional active ingredients
PRESENTATION AND DOSSAGE
VIAL(concent. for sol. for infus.+ stabilizer sol. for infus.): 1×35mcg
Treatment of adult patients with Philadelphia chromosome-negative relapsed or refractory B‑cell precursor acute lymphoblastic leukemia (ALL). Limitations of use: After failure of two previous treatments and with no CNS involvement.
No formal drug interaction studies have been performed. Results from an in vitro test in human hepatocytes suggest that blinatumomab did not affect CYP450 enzyme activities.
Initiation of blinatumomab treatment causes transient release of cytokines during the first days of treatment that may suppress CYP450 enzymes. Patients who are receiving medicinal products that are CYP450 and transporter substrates with a narrow therapeutic index should be monitored for adverse effects (e.g. warfarin) or drug concentrations (e.g. cyclosporine) during this time. The dose of the concomitant medicinal product should be adjusted as needed.
Hypersensitivity to the active substance or to any of the excipients. Breast-feeding.
Neurologic events: Neurologic events including events with a fatal outcome have been observed. Grade 3 (CTCAE version 4.0) or higher (severe or life-threatening) neurologic events following initiation of blinatumomab administration included encephalopathy, seizures, speech disorders, disturbances in consciousness, confusion and disorientation, and coordination and balance disorders. The median time from initiation of blinatumomab to onset of a neurologic event was 9 days. The majority of events resolved after treatment interruption.
Elderly patients experienced a higher rate of neurological toxicities, including cognitive disorder, encephalopathy, and confusion. Patients with a medical history of neurologic signs and symptoms (such as dizziness, hypoesthesia, hyporeflexia, tremor, dysesthesia, paresthesia, memory impairment) demonstrated a higher rate of neurologic events (such as tremor, dizziness, confusional state, encephalopathy and ataxia). The median time to onset of a neurologic event in these patients was 12 days.
Blincyto is indicated for treatment of adult patients with Philadelphia chromosome-negative relapsed or refractory B‑cell precursor acute lymphoblastic leukemia (ALL) with no CNS involvement.
There is a possibility of a higher risk of neurologic events in patients with a history or presence of clinically relevant central nervous system (CNS) pathology (e.g. epilepsy, seizure, paresis, aphasia, stroke, severe brain injuries, dementia, Parkinson’s disease, cerebellar disease, organic brain syndrome, psychosis). There is limited experience in these patients as they were excluded from clinical trials. There is limited experience with blinatumomab in patients with documented active ALL in the CNS or cerebrospinal fluid (CSF). However patients have been treated with blinatumomab in clinical studies after clearance of CSF blasts with CNS directed therapy (such as intrathecal chemotherapy). Therefore once the CSF is cleared, treatment with blinatumomab may be initiated.
Infections: In patients receiving blinatumomab, serious infections, including sepsis, pneumonia, bacteremia, opportunistic infections and catheter site infections have been observed, some of which were life‑threatening or fatal. Patients with Eastern Cooperative Oncology Group (ECOG) performance status at baseline of 2 experienced a higher incidence of serious infections compared to patients with ECOG performance status of < 2. There is limited experience with blinatumomab in patients with an active uncontrolled infection.
Tumor lysis syndrome: Tumor lysis syndrome (TLS), which may be life-threatening or fatal (grade ≥ 4) has been observed in patients receiving blinatumomab.
Appropriate prophylactic measures including aggressive hydration and anti-hyperuricaemia therapy (such as allopurinol or rasburicase) should be used for the prevention and treatment of TLS during blinatumomab treatment, especially in patients with higher leukocytosis or a high tumour burden. Patients should be closely monitored for signs or symptoms of TLS, including renal function and fluid balance in the first 48 hours after the first infusion. In clinical studies, patients with moderate renal impairment showed an increased incidence of TLS compared with patients with mild renal impairment or normal renal function. Management of these events may require either temporary interruption or discontinuation of blinatumomab.
Neutropenia and febrile neutropenia: Neutropenia and febrile neutropenia, including life-threatening cases, have been observed in patients receiving blinatumomab. Laboratory parameters (including, but not limited to white blood cell count and absolute neutrophil count) should be monitored routinely during blinatumomab infusion, especially during the first 9 days of the first cycle, and treated appropriately.
Elevated liver enzymes: Treatment with blinatumomab was associated with transient elevations in liver enzymes. The majority of the events were observed within the first week of treatment initiation and did not require interruption or discontinuation of blinatumomab.
Pancreatitis: Pancreatitis, life-threatening or fatal, has been reported in patients receiving blinatumomab in clinical trials and the post-marketing setting. High-dose steroid therapy may have contributed, in some cases, to the pancreatitis. Evaluate patients who develop signs and symptoms of pancreatitis. Management of pancreatitis may require either temporary interruption or discontinuation of blinatumomab.
Leukoencephalopathy including progressive multifocal leukoencephalopathy: Cranial magnetic resonance imaging (MRI) changes showing leukoencephalopathy have been observed in patients receiving blinatumomab, especially in patients with prior treatment with cranial irradiation and anti-leukemic chemotherapy (including systemic high dose methotrexate or intrathecal cytarabine). The clinical significance of these imaging changes is unknown.
See prescribing information for full details.
Different type of infections, pneumonia, sepsis, hematological adverse effects, insomnia, confusion, disorientation, tremor, headache, nausea, vomiting.
See prescribing information for full details.
Treatment should be initiated under the direction of and supervised by physicians experienced in the treatment of hematological malignancies. Hospitalization is recommended for initiation at a minimum for the first 9 days of the first cycle and the first 2 days of the second cycle. In patients with a history of clinically relevant central nervous system (CNS) pathology, hospitalization is recommended at a minimum for the first 14 days of the first cycle. In the second cycle, hospitalization is recommended at a minimum for 2 days, and clinical judgment should be based on tolerance to Blinatumomab in the first cycle. Caution should be exercised as cases of late occurrence of first neurological events in the second cycle have been observed. For all subsequent cycle starts and reinitiation (e.g. if treatment is interrupted for 4 or more hours), supervision by a healthcare professional or hospitalization is recommended. Blinatumomab infusion bags should be prepared to infuse over 24 hours, 48 hours, 72 hours, or 96 hours.
Recommended dose (for adult patients at least 45 kg in weight):
Cycle 1: Starting dose Days 1 – 7: 9 mcg/day via continuous infusion. Subsequent dose Days 8 – 28: 28 mcg/day via continuous infusion. 2 week-treatment free interval (Days 29 – 42).
Cycle 2 and subsequent cycles (Days 1 – 28): 28 mcg/day via continuous infusion.
Premedication and additional medication recommendations: Dexamethasone 20 mg intravenous should be administered 1 hour prior to initiation of each cycle of Blinatumomab therapy. Anti-pyretic use (e.g. paracetamol) is recommended to reduce pyrexia during the first 48 hours of each treatment cycle.
Intrathecal chemotherapy prophylaxis is recommended before and during Blinatumomab therapy to prevent central nervous system ALL relapse.
Pre-phase treatment for patients with high tumor burden: For patients with ≥ 50% leukemic blasts in bone marrow or > 15,000/microliter peripheral blood leukemic blast counts treat with dexamethasone (not to exceed 24 mg/day). Consideration to discontinue Blinatumomab temporarily or permanently as appropriate should be made in the case of the following severe (grade 3) or life-threatening (grade 4) toxicities: cytokine release syndrome, tumor lysis syndrome, neurological toxicity, elevated liver enzymes and any other clinically relevant toxicities.
If the interruption of treatment after an adverse event is no longer than 7 days, continue the same cycle to a total of 28 days of infusion inclusive of days before and after the interruption in that cycle. If an interruption due to an adverse event is longer than 7 days, start a new cycle. If the toxicity takes more than 14 days to resolve, discontinue Blinatumomab permanently.
For dose adjustment according to toxicity – See prescribing information for full details.
Elderly: No dose adjustment is necessary in elderly patients (≥ 65 years of age. There is limited experience with Blinatumomab in patients ≥ 75 years of age.
Renal impairment: Based on pharmacokinetic analyses, dose adjustment is not necessary in patients with mild to moderate renal dysfunction. The safety and efficacy of Blinatumomab have not been studied in patients with severe renal impairment.
Hepatic impairment: Based on pharmacokinetic analyses, no effect of baseline liver function on blinatumomab exposure is expected and adjustment of the initial dose is not necessary. The safety and efficacy of Blinatumomab have not been studied in patients with severe hepatic impairment.
Pediatric population: The safety and efficacy of Blinatumomab in pediatric patients have not yet been established.
Overdoses have been observed including one patient who received 133-fold the recommended therapeutic dose of Blinatumomab delivered over a short duration. Overdoses resulted in adverse reactions which were consistent with the reactions observed at the recommended therapeutic dose and included fever, tremors, and headache. In the event of overdose, the infusion should be temporarily interrupted and patients should be monitored. Reinitiation of Blinatumomab at the correct therapeutic dose should be considered when all toxicities have resolved and no earlier than 12 hours after interruption of the infusion.
PREGNANCY & LACTATION
Pregnancy: Reproductive toxicity studies have not been conducted with blinatumomab.
Lactation: It is unknown whether blinatumomab or metabolites are excreted in human milk.
See prescribing information for full details.
Storage: Store and transport refrigerated (2°C – 8°C). Do not freeze. Store the vials in the original package in order to protect from light. After removal from the refrigerator, this drug may be stored at room temperature (23-27°C) and used within 8 hours.
MANUFACTURER & DISTRIBUTER:
Manufacturer: Amgen Europe
License Holder: Amgen Europe