Chemistry:Elotuzumab

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Short description: Pharmaceutical drug
Elotuzumab
Monoclonal antibody
TypeWhole antibody
SourceHumanized
TargetSLAMF7 (CD319)
Clinical data
Trade namesEmpliciti
Other namesHuLuc63
License data
Pregnancy
category
  • AU: C
Routes of
administration		Intravenous
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability100% (IV)
Identifiers
CAS Number
IUPHAR/BPS
DrugBank
ChemSpider
  • none
UNII
KEGG
Chemical and physical data
FormulaC6476H9982N1714O2016S42
Molar mass145453.59 g·mol−1
 ☒N☑Y (what is this?)  (verify)

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.[2] 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.[2] Administration of elotuzumab is done intravenously.[2] Each intravenous injection of elotuzumab should be premedicated with dexamethasone, diphenhydramine, ranitidine and acetaminophen.[3] It is being developed by Bristol Myers Squibb and AbbVie.[4]

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.[2] The most common side effects of elotuzumab with pomalidomide and dexamethasone includes constipation and hyperglycemia.[2] There is no available information for the use of elotuzumab in pregnant women.[2]

Elotuzumab is an immunostimulatory antibody that targets the Signaling Lymphocytic Activation Molecule Family member 7 (SLAMF7) through two mechanisms.[2]

In May 2014, it was granted breakthrough therapy designation by the US Food and Drug Administration (FDA) (for multiple myeloma).[5] 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.[6] In May 2016 the EC/EU gave a similar approval.[7] Furthermore, the results of the ELOQUENT 3 study led to the FDA approval of elotuzumab in combination with pomalidomide and dexamethasone in 2018.[8]

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.[2] For medical use in multiple myeloma patients, elotuzumab can be combined with either lenalidomide and dexamethasone or pomalidomide and dexamethasone.[2]

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.[2] For additional information on dosing dexamethasone and/or lenalidomide, refer to the package inserts.[2]

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).[2] At the start of cycle 3, administer 20 mg/kg every 4 weeks, while administering the recommended dose of pomalidomide and low dose dexamethasone.[2] For additional information on dosing dexamethasone and/or dexamethasone, refer to the package inserts.[2]

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.[2][9][10] The most common adverse reactions (20% or higher) denoted in the elotuzumab treated patients in the study were:[2][9][10]

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.[2][11][12]

Mechanism of action

Elotuzumab is an immunostimulatory antibody that targets signaling lymphocyte activation molecule family member 7, also known as SLAMF7.[8] 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.[8]  

Elotuzumab works by activating the natural killer cells through the SLAMF7 pathway.[2][8] Along with that, the SLAMF7 of the myeloma cells are targeted and flagged, for natural killer cell-mediated destruction through antibody-dependent cellular toxicity.[2][8]

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.[9][10] This randomized, open-label, phase 3, multicenter trial studied patients 18 years and older with multiple myeloma and measurable disease.[9] 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.[9] The median progression-free survival for the elotuzumab group was 19.4 months compared with 14.9 months in the control group.[9] Additionally, the response rate for the etoluzumab group was 79%, compared to the control group with 66%.[9]

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.[11] The elotuzumab group, with 60 patients, received elotuzumab with pomalidomide and dexamethasone and the control group, with 57 patients, received pomalidomide and dexamethasone alone.[11] 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.[11] 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.[11]

References

  1. ↑ "Prescription medicines: registration of new chemical entities in Australia, 2016". 21 June 2022. https://www.tga.gov.au/prescription-medicines-registration-new-chemical-entities-australia-2016. 
  2. ↑ 2.00 2.01 2.02 2.03 2.04 2.05 2.06 2.07 2.08 2.09 2.10 2.11 2.12 2.13 2.14 2.15 2.16 2.17 2.18 "Elotuzumab Package Insert". https://packageinserts.bms.com/pi/pi_empliciti.pdf. 
  3. ↑ "Empliciti (elotuzumab) for Injection, for Intravenous Use. Full Prescribing Information". Princeton, New Jersey: Bristol-Myers Squibb Company. http://packageinserts.bms.com/pi/pi_empliciti.pdf. 
  4. ↑ "Bristol Myers Squibb Reports Primary Results of ELOQUENT-1 Study Evaluating Empliciti (elotuzumab) Plus Revlimid (lenalidomide) and Dexamethasone in Patients with Newly Diagnosed, Untreated Multiple Myeloma" (in en-US). https://news.bms.com/news/corporate-financial/2020/Bristol-Myers-Squibb-Reports-Primary-Results-of-ELOQUENT-1-Study-Evaluating-Empliciti-elotuzumab-Plus-Revlimid-lenalidomide-and-Dexamethasone-in-Patients-with-Newly-Diagnosed-Untreated-Multiple-Myeloma/default.aspx. 
  5. ↑ "Bristol-Myers Squibb and AbbVie Receive U.S. FDA Breakthrough Therapy Designation for Elotuzumab, an Investigational Humanized Monoclonal Antibody for Multiple Myeloma" (Press release). Princeton, New Jersey and North Chicago, Illinois: Bristol-Myers Squibb. 2014-05-19. Retrieved 2015-02-05.
  6. ↑ "Bristol-Myers Squibb and AbbVie Receive FDA Approval of Empliciti™ (elotuzumab) for the Treatment of Patients with Multiple Myeloma Who Have Received One to Three Prior Therapies" (in en-US). https://news.bms.com/news/details/2015/Bristol-Myers-Squibb-and-AbbVie-Receive-FDA-Approval-of-Empliciti-elotuzumab-for-the-Treatment-of-Patients-with-Multiple-Myeloma-Who-Have-Received-One-to-Three-Prior-Therapies/default.aspx. 
  7. ↑ BMS gets two new cancer approvals in Europe. May 2016
  8. ↑ 8.0 8.1 8.2 8.3 8.4 "U.S. Food and Drug Administration Approves Empliciti® (elotuzumab) Plus Pomalidomide and Dexamethasone, a New Immunotherapy Combination for Certain Patients with Relapsed or Refractory Multiple Myeloma" (in en-US). https://news.bms.com/news/details/2018/US-Food-and-Drug-Administration-Approves-Empliciti-elotuzumab-Plus-Pomalidomide-and-Dexamethasone-a-New-Immunotherapy-Combination-for-Certain-Patients-with-Relapsed-or-Refractory-Multiple-Myeloma/default.aspx. 
  9. ↑ 9.0 9.1 9.2 9.3 9.4 9.5 9.6 "Elotuzumab Therapy for Relapsed or Refractory Multiple Myeloma". The New England Journal of Medicine 373 (7): 621–631. August 2015. doi:10.1056/NEJMoa1505654. PMID 26035255. 
  10. ↑ 10.0 10.1 10.2 Clinical trial number NCT01239797 for "Phase III Study of Lenalidomide and Dexamethasone With or Without Elotuzumab to Treat Relapsed or Refractory Multiple Myeloma (ELOQUENT - 2)" at ClinicalTrials.gov
  11. ↑ 11.0 11.1 11.2 11.3 11.4 "Elotuzumab plus Pomalidomide and Dexamethasone for Multiple Myeloma". The New England Journal of Medicine 379 (19): 1811–1822. November 2018. doi:10.1056/NEJMoa1805762. PMID 30403938. 
  12. ↑ "Eloquent 3 Trial". 6 July 2020. https://clinicaltrials.gov/ct2/show/NCT02654132. 

External links



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