Английская Википедия:Elotuzumab
Шаблон:Short description Шаблон:Drugbox
Elotuzumab, sold under the brand name Empliciti, is a humanized IgG1 monoclonal antibody medication used in combination with lenalidomide and dexamethasone, for adults that have received 1 to 3 prior therapies for the treatment of multiple myeloma.[1] It is also indicated for adult patients in combination with pomalidomide and dexamethasone, who have received 2 prior therapies including lenalidomide and a protease inhibitor.[1] Administration of elotuzumab is done intravenously.[1] Each intravenous injection of elotuzumab should be premedicated with dexamethasone, diphenhydramine, ranitidine and acetaminophen.[2] It is being developed by Bristol Myers Squibb and AbbVie.[3]
Common side effects of elotuzumab with lenalidomide and dexamethasone includes fatigue, diarrhea, pyrexia, constipation, cough, peripheral neuropathy, nasopharyngitis, upper respiratory tract infection, decreased appetite, and pneumonia.[1] The most common side effects of elotuzumab with pomalidomide and dexamethasone includes constipation and hyperglycemia.[1] There is no available information for the use of elotuzumab in pregnant women.[1]
Elotuzumab is an immunostimulatory antibody that targets the Signaling Lymphocytic Activation Molecule Family member 7 (SLAMF7) through two mechanisms.[1]
In May 2014, it was granted breakthrough therapy designation by the US Food and Drug Administration (FDA) (for multiple myeloma).[4] The initial FDA approval of elotuzumab in 2015 in combination with lenalidomide and dexamethasone was carried out through the results illustrated in the ELOQUENT 2 study.[5] In May 2016 the EC/EU gave a similar approval.[6] Furthermore, the results of the ELOQUENT 3 study led to the FDA approval of elotuzumab in combination with pomalidomide and dexamethasone in 2018.[7]
Medical use
Multiple myeloma
Elotuzumab is indicated for adult patients in combination treatment for multiple myeloma in patients that have received 1 to 3 prior therapies.[1] For medical use in multiple myeloma patients, elotuzumab can be combined with either lenalidomide and dexamethasone or pomalidomide and dexamethasone.[1]
Dosage and administration
In combination with lenalidomide and dexamethasone
The package insert advises that intravenous administration with 10 mg/kg every week for the first 2 cycles (each cycle is 28 days) and every 2 weeks thereafter, with the appropriate doses of lenalidomide and low dose dexamethasone is acceptable for treatment.[1] For additional information on dosing dexamethasone and/or lenalidomide, refer to the package inserts.[1]
In combination with pomalidomide and dexamethasone
Elotuzumab is recommended through intravenous administration at 10 mg/kg each week for the first 2 cycles (each cycle is 28 days).[1] At the start of cycle 3, administer 20 mg/kg every 4 weeks, while administering the recommended dose of pomalidomide and low dose dexamethasone.[1] For additional information on dosing dexamethasone and/or dexamethasone, refer to the package inserts.[1]
Adverse effects
To evaluate the adverse reactions in the Eloquent 2 trial, elotuzumab was combined with lenalidomide and dexamethasone and compared with lenalidomide and dexamethasone alone.[1][8][9] The most common adverse reactions (20% or higher) denoted in the elotuzumab treated patients in the study were:[1][8][9]
- Fatigue, diarrhea, pyrexia, constipation, cough, peripheral neuropathy, nasopharyngitis, upper respiratory tract infection, decreased appetite, and pneumonia
Similarly, the adverse reactions in the Eloquent 3 trial were examined by comparing the elotuzumab combined with pomalidomide and dexamethasone with the pomalidomide and dexamethasone alone.[1][10][11]
Mechanism of action
Elotuzumab is an immunostimulatory antibody that targets signaling lymphocyte activation molecule family member 7, also known as SLAMF7.[7] SLAMF7 is a cell surface glycoprotein that is present on myeloma cells, natural killer cells, plasma cells, and subsets of immune cells of the hematopoietic lineage.[7]
Elotuzumab works by activating the natural killer cells through the SLAMF7 pathway.[1][7] Along with that, the SLAMF7 of the myeloma cells are targeted and flagged, for natural killer cell-mediated destruction through antibody-dependent cellular toxicity.[1][7]
Clinical trials
Eloquent 2 trial
The trial, Elotuzumab Therapy for Relapsed or Refractory Multiple Myeloma, also known as the Eloquent 2 trial, studied the efficacy and safety of elotuzumab. The objective of the study was to determine if the addition of elotuzumab with lenalidomide and dexamethasone would increase progression- free survival in patients with refractory multiple myeloma.[8][9] This randomized, open-label, phase 3, multicenter trial studied patients 18 years and older with multiple myeloma and measurable disease.[8] With 321 patients designated to the elotuzumab group and 325 to the control group, the elotuzumab group had a significant relative reduction in the risk of disease progression or death.[8] The median progression-free survival for the elotuzumab group was 19.4 months compared with 14.9 months in the control group.[8] Additionally, the response rate for the etoluzumab group was 79%, compared to the control group with 66%.[8]
Eloquent 3 trial
In the Eloquent 3 trial, also known as Elotuzumab plus Pomalidomide and Dexamethasone for Multiple Myeloma, 117 patients with refractory or relapsed multiple myeloma, and were refractory to lenalidomide and a protease inhibitor, were randomized to either the elotuzumab group or the control group.[10] The elotuzumab group, with 60 patients, received elotuzumab with pomalidomide and dexamethasone and the control group, with 57 patients, received pomalidomide and dexamethasone alone.[10] Among patients that had failed treatment with lenalidomide and a protease inhibitor, death or risk of progression was significantly lower in the elotuzumab study arm.[10] The median progression-free survival in the elotuzumab study arm was 10.3 months compared to 4.7 months in the control study group, after a 9.1 month follow up period.[10]
References
External links
Шаблон:Monoclonals for tumors Шаблон:Portal bar
- ↑ 1,00 1,01 1,02 1,03 1,04 1,05 1,06 1,07 1,08 1,09 1,10 1,11 1,12 1,13 1,14 1,15 1,16 1,17 1,18 Шаблон:Cite web
- ↑ Шаблон:Cite web
- ↑ Шаблон:Cite web
- ↑ Шаблон:Cite press release
- ↑ Шаблон:Cite web
- ↑ BMS gets two new cancer approvals in Europe. May 2016
- ↑ 7,0 7,1 7,2 7,3 7,4 Шаблон:Cite web
- ↑ 8,0 8,1 8,2 8,3 8,4 8,5 8,6 Шаблон:Cite journal
- ↑ 9,0 9,1 9,2 Шаблон:ClinicalTrialsGov
- ↑ 10,0 10,1 10,2 10,3 10,4 Шаблон:Cite journal
- ↑ Шаблон:Cite web
