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| Primary information |
|---|
| ID | 15720 |
| Therapeutic ID | Th1621 |
| Protein Name | Tafasitamab |
| Sequence | >Th1621_Tafasitamab
EVQLVESGGGLVKPGGSLKLSCAASGYTFTSYVMHWVRQAPGKGLEWIGYINPYNDGTKYNEKFQGRVTISSDKSISTAYMELSSLRSEDTAMYYCARGTYYYGTRVFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPDVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTFRVVSVLTVVHQDWLNGKEYKCKVSNKALPAPEEKTISKTKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPMLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
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| 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 |
| Patents Number | NA |
| Date of Issue | NA |
| Date of Expiry | NA |
| Drug Interaction | NA |
| Target | B-lymphocyte antigen CD19 |
| Brand Name | Minjuvi |
| Company | Incyte Corporation |
| Brand Description | Incyte Corporation |
| Prescribed For | Intravenous |
| Chemical Name | 200 mg / vial |
| Formulation | NA |
| Physical Appearance | The most common side effects with Minjuvi (which may affect more than 1 in 10 people) are infections, neutropenia (low white blood cell count), anaemia (low red blood cell count), thrombocytopaenia (low blood platelet count), diarrhoea, weakness, cough, peripheral oedema (swelling especially of the ankles and feet), fever and decreased appetite. |
| Route of Administration | Minjuvi can only be obtained with a prescription and must be given by a healthcare professional experienced in cancer treatment. The medicine is available as a powder to be made into a solution for infusion (drip) into a vein. |
| Recommended Dosage | Minjuvi is a cancer medicine used first in combination with another medicine called lenalidomide, and then on its own, to treat adults with diffuse large B-cell lymphoma (DLBCL) whose cancer has returned or has stopped responding to other treatments and who cannot have an autologous stem cell transplantation (a transplant where the stem cells are collected from the patients themselves). |
| Contraindication | NA |
| Side Effects | NA |
| Useful Link 1 | Link |
| Useful Link 2 | Link |
| Remarks | NA |