Now Available – New FDA-approvals for R/R B-Cell Precursor ALL Patients

• August 24, 2017
• News

The U.S. Food and Drug Administration (FDA) for BLINCYTO® (blinatumomab) has two recent approvals:

• On July 11, 2017, the FDA granted full approval to BLINCYTO® (blinatumomab) for the treatment of relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL) in adults and children, regardless of Philadelphia chromosome status.^1,2
• The FDA approved Amgen’s supplemental Biologics License Application (sBLA) for BLINCYTO® to include overall survival (OS) data from the Phase 3 TOWER study.
• Use of BLINCYTO® for up to four additional cycles of continued therapy was also approved with data from the TOWER study for a total of up to nine cycles of treatment.*
• The sBLA approval also included data from the Phase 2 ALCANTARA study supporting the treatment of patients with Philadelphia chromosome-positive (Ph+) relapsed or refractory B-cell precursor ALL.
• On May 3, 2017, the FDA also approved the 7-Day infusion option for BLINCYTO®3. This option is available for patients weighing greater than or equal to 22 kg and is not recommended for patients weighing less than 22 kg.²

*A treatment course consists of up to 2 cycles of BLINCYTO® for induction followed by 3 additional cycles for consolidation treatment.  Up to 4 cycles of continued therapy may be given following consolidation treatment for a total of up to 9 cycles of treatment.²

BLINCYTO® Product Highlights:

NDC has been “zero-filled” to ensure creation of an 11-digit code that meets HIPAA standards.⁵ The zero-fill location is indicated in bold.

HCPCS=Healthcare Common Procedure Coding System; HIPAA=Health Insurance Portability and Accountability Act; IV=intravenous; NDC=National Drug Code.

7-Day Infusion Option Highlights:

The table below summarizes the volume of reconstituted BLINCYTO® required to prepare the 7-Day infusion option.  For additional details, refer to Dosing and Administration sections 2.6 & 2.7 of the updated Prescribing Information for more information.²

BSA=body surface area; USP=United States Pharmacopeia.

For additional product questions regarding BLINCYTO®, please go to www.blincyto.com or contact Amgen Medical Information at 1-800-772-6436.

For all other questions, please contact Amgen Assist 360™ at 1-888-427-7478.

Please see below for the Indication and Important Safety Information for BLINCYTO®.

Complete information regarding dosing and administration, warnings, precautions, safety and efficacy, can be found in the full prescribing information by clicking here.

INDICATION

BLINCYTO® is indicated for the treatment of relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL) in adults and children.

IMPORTANT SAFETY INFORMATION

WARNING: CYTOKINE RELEASE SYNDROME and NEUROLOGICAL TOXICITIES

• Cytokine Release Syndrome (CRS), which may be life-threatening or fatal, occurred in patients receiving BLINCYTO®. Interrupt or discontinue BLINCYTO® as recommended. 
• Neurological toxicities, which may be severe, life-threatening or fatal, occurred in patients receiving BLINCYTO®. Interrupt or discontinue BLINCYTO® as recommended.

Contraindications

BLINCYTO® is contraindicated in patients with a known hypersensitivity to blinatumomab or to any component of the product formulation.

Warnings and Precautions 

• Cytokine Release Syndrome (CRS): CRS, which may be life-threatening or fatal, occurred in patients receiving BLINCYTO®. Infusion reactions have occurred and may be clinically indistinguishable from manifestations of CRS. Closely monitor patients for signs and symptoms of serious adverse events such as pyrexia, headache, nausea, asthenia, hypotension, increased alanine aminotransferase (ALT), increased aspartate aminotransferase (AST), and increased total bilirubin (TBILI). In some cases, disseminated intravascular coagulation (DIC), capillary leak syndrome (CLS), and hemophagocytic histiocytosis/macrophage activation syndrome (MAS) have been reported in the setting of CRS. Interrupt or discontinue BLINCYTO® as outlined in the Prescribing Information (PI).
• Neurological Toxicities: Approximately 65% of patients receiving BLINCYTO® in clinical trials experienced neurological toxicities. The median time to the first event was within the first 2 weeks of BLINCYTO® treatment and the majority of events resolved. The most common (≥ 10%) manifestations of neurological toxicity were headache and tremor. Severe, life-threatening, or fatal neurological toxicities occurred in approximately 13% of patients, including encephalopathy, convulsions, speech disorders, disturbances in consciousness, confusion and disorientation, and coordination and balance disorders. Monitor patients for signs or symptoms and interrupt or discontinue BLINCYTO® as outlined in the PI.
• Infections: Approximately 25% of patients receiving BLINCYTO® in clinical trials experienced serious infections such as sepsis, pneumonia, bacteremia, opportunistic infections, and catheter-site infections, some of which were life-threatening or fatal. Administer prophylactic antibiotics and employ surveillance testing as appropriate during treatment. Monitor patients for signs or symptoms of infection and treat appropriately, including interruption or discontinuation of BLINCYTO® as needed.
• Tumor Lysis Syndrome (TLS), which may be life-threatening or fatal, has been observed. Preventive measures, including pretreatment nontoxic cytoreduction and on-treatment hydration, should be used during BLINCYTO® treatment. Monitor patients for signs and symptoms of TLS and interrupt or discontinue BLINCYTO® as needed to manage these events.
• Neutropenia and Febrile Neutropenia, including life-threatening cases, have been observed. Monitor appropriate laboratory parameters (including, but not limited to, white blood cell count and absolute neutrophil count) during BLINCYTO® infusion and interrupt BLINCYTO® if prolonged neutropenia occurs.
• Effects on Ability to Drive and Use Machines: Due to the possibility of neurological events, including seizures, patients receiving BLINCYTO® are at risk for loss of consciousness, and should be advised against driving and engaging in hazardous occupations or activities such as operating heavy or potentially dangerous machinery while BLINCYTO® is being administered.
• Elevated Liver Enzymes: Transient elevations in liver enzymes have been associated with BLINCYTO® treatment with a median time to onset of 3 days.  In patients receiving BLINCYTO®, although the majority of these events were observed in the setting of CRS, some cases of elevated liver enzymes were observed outside the setting of CRS, with a median time to onset of 19 days. Grade 3 or greater elevations in liver enzymes occurred in approximately 7% of patients outside the setting of CRS and resulted in treatment discontinuation in less than 1% of patients.  Monitor ALT, AST, gamma-glutamyl transferase (GGT), and TBILI prior to the start of and during BLINCYTO® treatment. BLINCYTO® treatment should be interrupted if transaminases rise to > 5 times the upper limit of normal (ULN) or if TBILI rises to > 3 times ULN.
• Pancreatitis: Fatal pancreatitis has been reported in patients receiving BLINCYTO® in combination with dexamethasone in clinical trials and the post-marketing setting. Evaluate patients who develop signs and symptoms of pancreatitis and interrupt or discontinue BLINCYTO® and dexamethasone as needed.
• Leukoencephalopathy: Although the clinical significance is unknown, cranial magnetic resonance imaging (MRI) changes showing leukoencephalopathy have been observed in patients receiving BLINCYTO®, especially in patients previously treated with cranial irradiation and antileukemic chemotherapy.
• Preparation and administration errors have occurred with BLINCYTO® treatment. Follow instructions for preparation (including admixing) and administration in the PI strictly to minimize medication errors (including underdose and overdose).
• Immunization: Vaccination with live virus vaccines is not recommended for at least 2 weeks prior to the start of BLINCYTO® treatment, during treatment, and until immune recovery following last cycle of BLINCYTO®.
• Risk of Serious Adverse Reactions in Pediatric Patients due to Benzyl Alcohol Preservative: Serious and fatal adverse reactions including “gasping syndrome,” which is characterized by central nervous system depression, metabolic acidosis, and gasping respirations, can occur in neonates and infants treated with benzyl alcohol-preserved drugs including BLINCYTO® (with preservative). When prescribing BLINCYTO® (with preservative) for pediatric patients, consider the combined daily metabolic load of benzyl alcohol from all sources including BLINCYTO® (with preservative) and other drugs containing benzyl alcohol. The minimum amount of benzyl alcohol at which serious adverse reactions may occur is not known. Due to the addition of bacteriostatic saline, 7-day bags of BLINCYTO® solution for infusion with preservative contain benzyl alcohol and are not recommended for use in any patients weighing < 22 kg.

Adverse Reactions

• The most common adverse reactions (≥ 20%) in clinical trial experience of patients with Philadelphia chromosome-negative relapsed or refractory B-cell precursor ALL (TOWER Study) treated with BLINCYTO® were infections (bacterial and pathogen unspecified), pyrexia, headache, infusion-related reactions, anemia, febrile neutropenia, thrombocytopenia, and neutropenia. Serious adverse reactions were reported in 62% of patients. The most common serious adverse reactions (≥ 2%) included febrile neutropenia, pyrexia, sepsis, pneumonia, overdose, septic shock, CRS, bacterial sepsis, device related infection, and bacteremia.
• Adverse reactions that were observed more frequently (≥ 10%) in the pediatric population compared to the adult population were pyrexia (80% vs. 61%), hypertension (26% vs. 8%), anemia (41% vs. 24%), infusion-related reaction (49% vs. 34%), thrombocytopenia (34% vs. 21%), leukopenia (24% vs. 11%), and weight increased (17% vs. 6%).
• In pediatric patients less than 2 years old (infants), the incidence of neurologic toxicities was not significantly different than for the other age groups, but its manifestations were different; the only event terms reported were agitation, headache, insomnia, somnolence, and irritability. Infants also had an increased incidence of hypokalemia (50%) compared to other pediatric age cohorts (15-20%) or adults (17%).

Dosage and Administration Guidelines 

• BLINCYTO® is administered as a continuous intravenous infusion at a constant flow rate using an infusion pump which should be programmable, lockable, non-elastomeric, and have an alarm.
• It is very important that the instructions for preparation (including admixing) and administration provided in the full Prescribing Information are strictly followed to minimize medication errors (including underdose and overdose).

Please click here for full Prescribing Information, including BOXED WARNINGS and Medication Guide, for BLINCYTO®.

BLINCYTO® is a trademark of Amgen Inc.

References:

1. Food and Drug Administration. BLA 125557/S-008 Supplement Approval.

https://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm566708.htm.  Accessed July 14, 2017

2. BLINCYTO^® (blinatumomab) Prescribing Information, Amgen.
3. Food and Drug Administration. BLA 125557/S-007 Supplement Approval. https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2017/125557Orig1s007ltr.pdf. Accessed July 14, 2017
4. Centers for Medicare and Medicaid Services. 2017 Table of Drugs. https://www.cms.gov/Medicare/Coding/HCPCSReleaseCodeSets/Downloads/2017-Table-of-Drugs.pdf. Accessed July 27, 2017.
5. Food and Drug Administration. National Drug Code Database Background Information. https://www.fda.gov/drugs/developmentapprovalprocess/ucm070829. Accessed July 14, 2017. 

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