Blinatumomab is a BiTE-class (bi-specific T-cell engagers) constructed monoclonal antibody indicated for the treatment of Philadelphia chromosome-negative relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL). Blinatumomab is manufactured by Amgen Inc. and marketed under the brand Blincyto™. A full treatment regimen consisting of two cycles of four weeks each, is priced at $178 000 USD. Blinatumomab was approved in December 2014 under the FDA’s accelerated approval program, which allows approval of a drug to treat a serious or life-threatening disease based on clinical data showing the drug has an effect on a surrogate endpoint reasonably likely to predict clinical benefit to patients.
|Protein chemical formula||C2367H3577N649O772S19|
|Protein average weight||54100.0 Da|
>single chain variable fragment fusion protein
QWSSNPLTFGAGTKLELKHHHHHHDownload FASTA Format
|External Identifiers |
- MEDI 538
- MT 103
|Approved Prescription Products|
|Name||Dosage||Strength||Route||Labeller||Marketing Start||Marketing End|
|Blincyto||kit||intravenous||Amgen Inc||2014-12-18||Not applicable||US|
|Blincyto||powder for solution||38.5 mcg||intravenous||Amgen Canada Inc||2016-03-17||Not applicable||Canada|
|Approved Generic Prescription Products||Not Available|
|Approved Over the Counter Products||Not Available|
|Unapproved/Other Products ||Not Available|
|International Brands||Not Available|
|Brand mixtures||Not Available|
|Super Class||Organic Acids|
|Class||Carboxylic Acids and Derivatives|
|Sub Class||Amino Acids, Peptides, and Analogues|
|Alternative Parents||Not Available|
|Molecular Framework||Not Available|
|External Descriptors||Not Available|
|Indication||Indicated for the treatment of Philadelphia chromosome-negative relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL).|
|Mechanism of action||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.|
|Volume of distribution|
4.52 L, standard deviation 2.89.
|Protein binding||Not Available|
The metabolic pathway of blinatumomab has not been characterized. Like other protein therapeutics, blinatumomab is expected to be degraded into small peptides and amino acids via catabolic pathways.
|Route of elimination||Not Available|
|Half life||2.11 hours, standard deviation 1.42. |
2.92 L/hour, standard deviation 2.83.
|Toxicity||- Cytokine Release Syndrome (CRS), which may be life-threatening or fatal, occurred in patients receiving blinatumomab. Interrupt or discontinue blinatumomab as recommended.
- Neurological toxicities, which may be severe, life-threatening, or fatal, occurred in patients receiving blinatumomab. Interrupt or discontinue blinatumomab as recommended.
- In patients receiving blinatumomab in clinical trials, serious infections such as sepsis, pneumonia, bacteremia, opportunistic infections, and catheter-site infections were observed in approximately 25% of patients, some of which were life-threatening or fatal.
- Tumor lysis syndrome (TLS), which may be life-threatening or fatal, has been observed in patients.
- Neutropenia and febrile neutropenia, including life-threatening cases, have been observed in patients.
- Treatment with blinatumomab was associated with transient elevations in liver enzymes.
- 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 antileukemic chemotherapy (including systemic high-dose methotrexate or intrathecal cytarabine).|
|SNP Mediated Effects||Not Available|
|SNP Mediated Adverse Drug Reactions||Not Available|
|Powder for solution||intravenous||38.5 mcg|
|Experimental Properties||Not Available|
|Synthesis Reference||Not Available|
- Zugmaier G, Klinger M, Schmidt M, Subklewe M: Clinical overview of anti-CD19 BiTE((R)) and ex vivo data from anti-CD33 BiTE((R)) as examples for retargeting T cells in hematologic malignancies. Mol Immunol. 2015 Oct;67(2 Pt A):58-66. doi: 10.1016/j.molimm.2015.02.033. Epub 2015 Apr 13. [PubMed:25883042 ]
- Garber K: Bispecific antibodies rise again. Nat Rev Drug Discov. 2014 Nov;13(11):799-801. doi: 10.1038/nrd4478. [PubMed:25359367 ]
|AHFS Codes||Not Available|
|PDB Entries||Not Available|
|FDA label||Download (242 KB) |
|Clozapine||The risk or severity of adverse effects can be increased when Blinatumomab is combined with Clozapine.|
|Denosumab||The risk or severity of adverse effects can be increased when Denosumab is combined with Blinatumomab.|
|Leflunomide||The risk or severity of adverse effects can be increased when Blinatumomab is combined with Leflunomide.|
|Metamizole||The risk or severity of adverse effects can be increased when Metamizole is combined with Blinatumomab.|
|Natalizumab||The risk or severity of adverse effects can be increased when Blinatumomab is combined with Natalizumab.|
|Pimecrolimus||The risk or severity of adverse effects can be increased when Pimecrolimus is combined with Blinatumomab.|
|Roflumilast||Roflumilast may increase the immunosuppressive activities of Blinatumomab.|
|Sipuleucel-T||The therapeutic efficacy of Sipuleucel-T can be decreased when used in combination with Blinatumomab.|
|Tacrolimus||The risk or severity of adverse effects can be increased when Tacrolimus is combined with Blinatumomab.|
|Tofacitinib||Blinatumomab may increase the immunosuppressive activities of Tofacitinib.|
|Trastuzumab||Trastuzumab may increase the neutropenic activities of Blinatumomab.|
|Food Interactions||Not Available|