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| Primary information |
|---|
| ID | 15722 |
| Therapeutic ID | Th1621 |
| Protein Name | Tafasitamab |
| Sequence | >Th1621_Tafasitamab
EVQLVESGGGLVKPGGSLKLSCAASGYTFTSYVMHWVRQAPGKGLEWIGYINPYNDGTKYNEKFQGRVTISSDKSISTAYMELSSLRSEDTAMYYCARGTYYYGTRVFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPDVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTFRVVSVLTVVHQDWLNGKEYKCKVSNKALPAPEEKTISKTKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPMLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
|
| Molecular Weight | 150000 |
| Chemical Formula | NA |
| Isoelectric Point | NA |
| Hydrophobicity | NA |
| Melting point | NA |
| Half-life | The terminal elimination half-life of tafasitamab is approximately 17 days.[L15292] |
| Description | Tafasitamab is a humanized, CD19-directed cytolytic monoclonal antibody intended for the treatment of B-cell malignancies.[L15302] It is produced using recombinant DNA technology in Chinese hamster ovary cells, and contains an IgG1/2 hybrid Fc-domain which has been modified with 2 amino acid substitutions to enhance its cytotoxicity relative to non-engineered anti-CD19 antibodies.[L15292,A191829] The CD19 surface protein is highly expressed on the surface of B-cells, where it appears to play a role in enhancing B-cell receptor signaling.[L15302] Its relative ubiquity across different stages of B-cell development, including pre-B and mature B-lymphocytes,[L15292] as well as its presence in several B-cell malignancies (e.g. chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), diffuse large B-cell lymphoma (DLBCL))[L15302] has made it a desirable target in the treatment these B-cell malignancies. Tafasatimab is designed to bind to and block the activity of the CD19 surface antigen, which ultimately results in the lysis of B-cells (both healthy and malignant).[L15292] Having previously received Breakthrough Therapy, Fast Track, and Orphan designations from the FDA,[A191829] tafasatimab-cxix (Monjuvi®) received an accelerated approval on July 31st, 2020, for the treatment of relapsed or refractory DLBCL in adult patients who cannot receive autologous stem cell transplants.[L15307] It must be used in combination with [lenalidomide], as this combination results in greater efficacy as compared to either agent alone.[L15292] |
| Indication/Disease | Tafasitamab is indicated, in combination with [lenalidomide], for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) not otherwise specified whom are ineligible for autologous stem cell transplant (ASCT).[L15292] |
| Pharmacodynamics | Tafasitamab induces a reduction in circulating B-cell counts by binding to a surface antigen, CD19, which is important for their survival.[L15302] Patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) experienced a 97% reduction in peripheral blood B-cell counts following 8 days of treatment, with a 100% reduction reached within 16 weeks of treatment.[L15292] Tafasitamab can cause infusion-related reactions, particularly during the initial cycles of therapy. Symptoms may include chills, flushing, dyspnea, and hypertension. Patients may be administered premedications (such as [acetaminophen], antihistamines, or glucocorticoids) 0.5 - 2 hours prior to infusion to minimize infusion-related reactions.[L15292] Tafasitamab may also cause significant myelosuppression, and subsequent infection, due to its mechanism of action - patients should undergo monitoring throughout therapy for signs of myelosuppression and/or infection.[L15292] |
| Mechanism of Action | The CD19 surface antigen is a protein expressed on the surface of pre-B and mature B-lymphocytes[L15292] that appears to play a role in enhancing B-cell receptor signaling and is considered integral to their survival.[L15302] These surface proteins are also highly expressed on several B-cell malignancies, such as chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), and diffuse large B-cell lymphoma (DLBCL).[L15302] Tafasitamab is a CD19-directed cytolytic monoclonal antibody that, upon binding and blocking the activity of CD19, causes lysis of B-cells. This process is mediated through both direct apoptosis and immune-mediated effector mechanisms, such as antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP).[L15292] |
| Toxicity | Data regarding overdose of tafasitamab are unavailable. Symptoms of overdosage are likely to be consistent with its adverse effect profile, and may therefore involve significant infusion-related reactions and/or myelosuppression.[L15292] |
| Metabolism | The biotransformation of tafasitamab has not been elucidated. Most monoclonal antibodies undergo intracellular catabolism via lysosomal degradation to smaller amino acids and peptides.[A19126,A216712] |
| Absorption | Following intravenous administration of tafasitamab 12 mg/kg on Days 1, 8, 15, and 22 in cycle(s) 1-3 (with an additional dose on Day 4 of cycle 1), mean trough concentrations were 179 (± 53) µg/mL. From cycle 4 onwards, which involve the administration of tafasitamab 12 mg/kg on Days 1 and 15, mean trough concentrations were 153 (± 68) µg/mL.[L15292] The overall maximum tafasitamab serum concentrations reached were 483 (± 109) µg/mL.[L15292] |
| The total volume of distribution of tafasitamab following intravenous injection is approximately 9.3 L.[L15292] |
| Clearance | The clearance of tafasitamab is approximately 0.41 L/day.[L15292] |
| Categories | Antibodies, Monoclonal, Humanized |
| Patents Number | NA |
| Date of Issue | NA |
| Date of Expiry | NA |
| Drug Interaction | NA |
| Target | B-lymphocyte antigen CD19 |
| Brand Name | NA |
| Company | NA |
| Brand Description | NA |
| Prescribed For | NA |
| Chemical Name | NA |
| Formulation | NA |
| Physical Appearance | NA |
| Route of Administration | NA |
| Recommended Dosage | NA |
| Contraindication | NA |
| Side Effects | NA |
| Useful Link 1 | Link |
| Useful Link 2 | NA |
| Remarks | NA |