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Empliciti

Friday, September 30, 2016   (1 Comments)
Posted by: Elizabeth Maynard
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Marijanel Villamayor Alilio, PharmD Candidate 2018
Thao K. Huynh, PharmD, BCOP
University of Pittsburgh School of Pharmacy

 Multiple myeloma is a plasma cell cancer usually associated with increased levels of monoclonal immunoglobulin, anemia, hypercalcemia, lytic bone lesions, and renal failure. Development of multiple myeloma can also result in inadequate immune response leading to infections, injuries to the bone, the formation of multiple plasmacytomas, nerve damage, hyperviscosity of the blood, and light-chain amyloidosis.1 No differentiating symptoms are usually seen in patients until the disease has progressed to an advanced stage, which makes it difficult to diagnose, but bone pain and fatigue are common.1,2 Current treatments available to treat active multiple myeloma include conventional chemotherapy, corticosteroids, immunomodulating agents, proteosome inhibitors, histone deacetylase inhibitors, and monoclonal antibodies.3 On average, the five-year relative survival rate is about 40% which can be extended to eight years for patients whom are transplant-eligible.1

Elotuzumab (Empliciti™), approved by the Food and Drug Administration in November of 2015, is indicated for use in combination with lenalidomide and dexamethasone in patients who have already had one to three prior therapies. The National Comprehensive Cancer Network Clinical Practice Guidelines listed elotuzumab as one of the preferred, category 1 treatment option for patients with multiple myeloma who have received one to three prior therapies.4 Elotuzumab, a monoclonal antibody, works by targeting the signaling lymphocyte activation molecule family member 7 (SLAMF7) glycoprotein, also known as surface antigen CD319, which is expressed on plasma cells, natural killer cells, and myeloma cells. By targeting this protein, natural killer cells are activated, and myeloma cells are tagged for recognition, thus promoting cytotoxicity against multiple myeloma cells.5

Elotuzumab was approved based on the ELOQUENT-2 study, a randomized, open-label, multi-center, phase three trial. Subjects included patients 18 years and older, had multiple myeloma and measurable disease, received one to three previous therapies with documented disease progression, and had creatinine clearances of 30 ml/min or higher. Patients were randomized to either the elotuzumab or control group. The elotuzumab group received therapy on 28-day cycles. For the first two cycles, elotuzumab 10 mg/kg IV were administered weekly. Starting with the third cycle onward, elotuzumab was administered once every other week. On days without elotuzumab administration, dexamethasone 40 mg PO was given, and on days with elotuzumab administration, dexamethasone 8 mg IV and 28 mg PO were administered. Lenalidomide 25 mg PO was administered for the first three weeks of each 28-day cycle. The control group followed the standard of care consisting of lenalidomide 25 mg PO daily for the first three weeks and 40 mg dexamethasone PO weekly on a 28-day cycle. Treatment continued until disease progression, unacceptable toxicity, or withdrawal of consent. Coprimary endpoints were progression-free survival and overall response rate. Secondary endpoints were overall survival, severity of pain, and interference with daily life. Results of the primary endpoints of the study demonstrated a median progression-free survival after two years of 19.4 months in the elotuzumab group compared to 14.9 months for those in the control group, HR 0.70, p < 0.001. Overall response rate was greater in the elotuzumab group: 79% versus 66%, p < 0.001. The secondary endpoint of overall survival is still to be determined since the criteria has not been met for data analysis. In addition, results showed that were no statistical differences in pain severity and interference with daily activities.6

Notable side effects exhibited in the elotuzumab group include grade 3 or 4 lymphocytopenia. Neutropenia was exhibited to a greater extent in the elotuzumab arm, however, the rates of grade 3 to 4 toxicity were similar between both arms. The only other side effect more prevalent in the elotuzumab arm include cough. Other side effects were similar between both arms of the study.6

Elotuzumab is currently available only as an intravenous powder for solution in 300 and 400 mg vials. The recommended administration of elotuzumab with lenalidomide and dexamethasone can follow the 28-day cycle as detailed in Table 1. Premedication with dexamethasone, H1 blockers, H2 blockers, and acetaminophen are required 45 to 90 minutes prior to the start of the elotuzumab administration. In the event that a dose of a premedication is delayed, interrupted, or discontinued, H1 blockers, H2 blockers, and acetaminophen can be continued as scheduled; in cases involving dexamethasone, the prescriber must decide whether or not to administer elotuzumab based on clinical judgment due to the risk of hypersensitivity. There are no contraindications for using elotuzumab. Warnings and precautions associated with elotuzumab include: infusion reactions, infections, second primary malignancies, hepatotoxicities, and interference with determination of complete response. Drug-drug interactions have yet to be determined for elotuzumab.7

Table 1: Recommended Dosing Schedule of Elotuzumab in Combination with Lenalidomide and Dexamethasone

Cycle

28-Day Cycles 1 and 2

28-Day Cycles 3+

Day of Cycle

1

8

15

22

1

8

15

22

Premedication

 

 

Elotuzumab (mg/kg) IV

10

10

10

10

10

 

10

 

Lenalidomide (25 mg) PO

Days 1-21

Days 1-21

Dexamethasone (mg) PO*

28

28

28

28

28

40

28

40

Dexamethasone (mg) IV**

8

8

8

8

8

 

8

 

*Given 3-24 hours prior to elotuzumab administration

**Alternative premedications include: 25-50 mg diphenhydramine IV or PO, 50 mg ranitidine IV, 650-100 mg acetaminophen PO, or any equivalents

Adapted from the elotuzumab monograph.7

References

1.     Rathore B. Ferri’s clinical advisor. 2017 ed. Amsterdam: Elsevier, Inc; 2016. Multiple Myeloma; p. 821-4.

2.     Rajkumar S, Kumar S. Multiple Myeloma: Diagnosis and Treatment. Mayo Clin Proc. 2016 Jan; 99(1):101-19.

3.     Palumbo A, Anderson K. Multiple myeloma. N Engl J Med. 2011 Mar 17;364(11):1046-60.

4.     Anderson KC. NCCN Guidelines Update for Multiple Myeloma. J Natl Compr Canc Netw. 2016 May;14(5 Suppl):675-7.

5.     Collins S, Bakan C, Swartzel G, et al. Elotuzumab directly enhances NK cell cytotoxicity against myeloma via CS1 ligation: evidence for augmented NK cell function complementing ADCC. Cancer Immunol Immunother. 2013 Dec;62(12);1841–9.

6.     Lonial S, Dimopoulos M, Palumbo A, et al. Elotuzumab Therapy for Relapsed or Refractory Multiple Myeloma. N Engl J Med. 2015 Aug 15;373(7);621-31.

  1. Empliciti™ [package insert]. New York, NY. Bristol-Myerrs Squibb; 2015.

Comments...

Chantel Farrello says...
Posted Saturday, October 15, 2016
Hi Janel, Thanks for the information! Chantel Farrello, RPh

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