Elotuzumab
| Elotuzumab | ||
|---|---|---|
| Mass / length primary structure | 148 100.0 Da | |
| Identifier | ||
| External IDs |
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| Drug information | ||
| ATC code | L01 XC23 | |
| DrugBank | DB06317 | |
| Drug class | Monoclonal antibodies , antineoplastic agents | |
Elotuzumab is a monoclonal antibody and is used as a drug in the treatment of multiple myeloma in certain patients.
Chemistry and properties
Elotuzumab is a humanized recombinant IgG1- type antibody . The paratope comes from the mouse antibody MuLuc63. It is produced from mouse myeloma cells (NS0 cells) using recombinant DNA technology .
pharmacology
background
Multiple myeloma is a cancer belonging to the class of non-Hodgkin lymphomas . It is based on a malignant, degenerate cell clone of a B lymphocyte . It is characterized by a diffuse penetration of the bone marrow with activated B lymphocytes ( plasma cells ) and the production of pathological immunoglobulins . The glycoprotein SLAMF7 (Signaling Lymphocyte Activation Molecule Family Member 7, CD 319) is formed on the surface of myeloma cells and certain immune cells, the natural killer cells (NK cells) .
- → see also main article multiple myeloma
SLAMF7 is found on various immune cells, but is absent on the surface of blood stem cells and in healthy tissue.
Mechanism of action
SLAMF7 serves as a target for elotuzumab, which is specifically directed against SLAMF7. The binding to SLAMF7 on the surface of the myeloma cells marks them for NK cells. The interaction between myeloma and NK cells is facilitated and as a result, NK cells initiate the death of the myeloma cells through antibody-dependent cell-mediated cytotoxicity . In addition, NK cells are activated via the Fc signaling pathway ; NK and myeloma cells are brought together when elotuzumab binds to the Fc receptor of the killer cells and SLAMF7 of the myeloma cells.
Pharmacokinetics
At a dose of 10 mg / kg body weight and steady state (in combination with lenalidomide and dexamethasone) the volume of distribution is approximately 6.02 liters, the total clearance is 0.194 l / day. The clearance is non-linear and decreases with increasing dose. After discontinuation, a wash-out of 97 percent takes place over a period of three months .
application
Elotuzumab is indicated in adult patients with multiple myeloma. At least one further therapy must have failed beforehand. It is used in the form of an intravenous infusion , several times in 28-day cycles. The standard dose is 10 mg / kg body weight . The therapy takes place together with lenalidomide ( orally ). Dexamethasone , H1 anihistamines , H2 antihistamines and antipyretics are recommended as premedication to prevent side effects . Elotuzumab therapy will continue until the disease progresses or unacceptable side effects occur.
effectiveness
The phase III ELOQUENT-2 study showed the following results: Elotuzumab in combination with lenalidomide and dexamethasone reduced the progression (progression) or fatal outcome by 32 percent compared with therapy with lenalidomide and dexamethasone alone . Progression-free survival was improved by 21 percent (1 year) and 50 percent (2 years), respectively. The overall response rate to therapy with lenalidomide and dexamethasone alone was also increased (78.5 versus 65.5 percent). Elotuzumab is currently rated as a leap innovation (Pharm. Ztg.).
unwanted effects
More common side effects of elotuzumab are diarrhea , various effects that are associated with influencing the immune system ( e.g. herpes zoster , nasopharyngitis , flu , pneumonia ), lymphopenia and weight loss. The risk of deep vein thrombosis is increased. The risk of secondary primary malignancies (tumors that develop in the course of therapy) seems to be increased, although this is already increased even under monotherapy with lenalidomide. Despite premedication, infusion-related reactions can occasionally occur, which require more intensive monitoring of the patient's vital parameters.
Finished medicinal products
Elotuzumab was approved in the USA in 2015 and in the European Union and Switzerland in 2016. It is marketed by Bristol-Myers Squibb under the trade name Empliciti ® . The medicinal product contains powder (equivalent to 300 or 400 mg elotuzumab) for a concentrate for solution for infusion. The costs (Germany, as of 2019) for a vial are EUR 1,171.63 (300 mg) or EUR 1,557.58 (400 mg).
Individual evidence
- ↑ a b c Entry on elotuzumab in the DrugBank of the University of Alberta , accessed August 11, 2019.
- ↑ a b c d Bristol-Myers Squibb , drug prescribing information for Empliciti ® ( link ( page not available , search in web archives ) Info: . The link was automatically marked as defective Please review the link according to instructions and then remove this notice. , Called on August 11, 2019; restricted access)
- ↑ Hildebrandt et al .: Pschyrembel - Clinical Dictionary , Walter de Gruyter, 261st edition, pp. 1280-1281. ISBN 978-3-11-018534-8 .
- ↑ a b c d e f g h Pharm. Ztg. Online, drug profile : Elotuzumab (accessed on August 11, 2019)
- ↑ a b PharmaWiki.ch: Elotuzumab (accessed on August 11, 2019)
- ↑ Empliciti ® in Rote Liste online ( link , accessed August 11, 2019; restricted access)
