| Coverage Policy Manual | |
| Policy #: | 2017013 |
| Category: | Pharmacy |
| Initiated: | April 2017 |
| Last Review: | April 2023 |
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| Elotuzumab (e.g., Empliciti™) | |
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| Description: |
Elotuzumab is a monoclonal antibody that targets the Signaling Lymphocytic Activation Molecule Family member 7 (SLAMF7) protein and directly activates natural killer cells and facilitates the killing of myeloma cells through antibody-dependent cellular cytotoxicity. (Clinical Pharmacology, 2017).
Regulatory Status
Elotuzumab (e.g., Empliciti™) was FDA-approved in 2015. (U.S. Food and Drug Administration 2015).
On 11/2018 a new indication was added to Elotuzumab for use in combination with pomalidomide and dexamethasone.
Coding
See CPT/HCPCS Code section below.
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Policy/ Coverage: |
Effective August 1, 2021, for members of plans that utilize an oncology benefits management program, Prior Approval is required for this service and is managed through the oncology benefits management program.
Effective November 1, 2021
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
Elotuzumab meets member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes for the treatment of multiple myeloma for relapse or progressive disease when:
Off-label
The use of this drug is covered if a FDA-approved oncologic indication exists (not listed as an indication above) with the member meeting all of the additional requirements of the prescribing information (package insert listed in the “Indications and Usage”) AND/OR a NCCN category 1 or 2A recommendation is recognized in the NCCN Drugs and Biologics Compendium with the member meeting specified criteria (See policy #2000030).
Dosing and Administration
Dosing per FDA Guidelines
Recommended dosing for Elotuzumab in combination with lenalidomide and dexamethasone.
The prescribed regimen must be in compliance with FDA-approved dosing, with a dosing regimen 10mg/kg weekly for 2 weeks, then 10mg/kg every 2 weeks thereafter.
Recommended dosing for Elotuzumab in combination with pomalidomide and dexamethasone.
The prescribed regimen must be in compliance with FDA-approved dosing, with a dosing regimen 10mg/kg weekly for 2 cycles (28-day cycle). Starting at cycle 3 (28-day cycle), administer 20 mg/kg IV every 4 weeks.
Elotuzumab is available as 300 mg or 400 mg lyophilized powder in a single-dose vial for reconstitution.
Please refer to a separate policy on Site of Care or Site of Service Review policy #2018030 for pharmacologic/biologic medications.
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
The use of Elotuzumab for any indication or circumstance other than those outlined above does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectivenss in improving health outcomes.
For members with contracts without primary coverage criteria, the use of Elotuzumab for the treatment of any other indications or any other circumstances than those outlined above is considered investigational.
Investigational services are specific contract exclusions in most member benefit certificates of coverage.
Effective April 2019 to October 31, 2021
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage
Criteria
Elotuzumab meets member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness for the treatment of multiple myeloma.
Off-label
NCCN Category 1, 2a and 2b recommendations in accordance with Coverage Policy #2000030.
Dosing
Recommended dosing for Elotuzumab in combination with lenalidomide and dexamethasone.
The prescribed regimen must be in compliance with FDA-approved dosing, with a dosing regimen 10mg/kg weekly for 2 weeks, then 10mg/kg every 2 weeks thereafter.
Recommended dosing for Elotuzumab in combination with pomalidomide and dexamethasone.
The prescribed regimen must be in compliance with FDA-approved dosing, with a dosing regimen 10mg/kg weekly for 2 cycles (28-day cycle). Starting at cycle 3 (28-day cycle), administer 20 mg/kg IV every 4 weeks.
Please refer to a separate policy on Site of Care or Site of Service Review policy #2018030 for pharmacologic/biologic medications.
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary
Coverage Criteria
The use of Elotuzumab for the treatment of any other indications or any other circumstances than those outlined above does not meet member benefit certificate primary coverage criteria.
For members with contracts without primary coverage criteria, the use of Elotuzumab for the treatment of any other indications or any other circumstances than those outlined above is considered investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
Effective prior to April 2019
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage
Criteria
Elotuzumab meets primary coverage criteria and is covered for the following listed indications:
FDA labeled
Off-label (2017)
Dosing:
The prescribed regimen must be in compliance with FDA-approved dosing, with a dosing regimen of less than 10mg/kg weekly for 2 weeks, then 10mg/kg every 2 weeks thereafter.
Elotuzumab is given as an IV infusion at a rate of 2ml/min.
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary
Coverage Criteria
The use of Elotuzumab for the treatment of any other indications or any other circumstances than those outlined above does not meet member benefit certificate primary coverage criteria.
For members with contracts without primary coverage criteria, the use of Elotuzumab for the treatment of any other indications or any other circumstances than those outlined above is considered investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
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| Rationale: |
Elotuzumab was evaluated in a proof-of-concept, open-label phase 2 study in which 150 patients were randomly assigned to receive either elotuzumab with bortezomib and dexamethasone (EBd) or bortezomib and dexamethasone (Bd). Patients were aged 18 years or older with a confirmed diagnosis of multiple myeloma and had documented progression after 1 to 3 prior lines of therapy. The study met its primary endpoint of PFS with a 28% reduction in the risk of progression or death with EBd compared with Bd. Median PFS was 9.7 months with EBd vs 6.9 months with Bd. The 1 year PFS rate was 39% with EBd vs 33% with Bd. Overall response rate for the elotuzumab group was 66% for the EBd vs 63% for the Bd group. Adverse event reporting was similar in both arms of the study. For the EBd group, AEs were reported at 100% while the BD group reported 96% AEs. The most common grade 3 or higher AEs were infections and thrombocytopenia. Thrombocytopenia occurred less in the EBd group (9%) than the Bd group (17%). (Jakubowiak, 2016)
The safety and efficacy of elotuzumab in combination with lenalidomide and dexamethasone were evaluated in a randomized, open-label trial in patients with multiple myeloma who had received one to three prior therapies and had documented progression following their most recent therapy. A total of 646 patients were randomized in a 1:1 ratio to receive either elotuzumab in combination with lenalidomide and low-dose dexamethasone or lenalidomide and low-dose dexamethasone. The median PFS for the elotuzumab group was 19.4 months while the standard treatment group PFS was 14.9 months. ORR was 78.5% (14 complete responses, 91 very good partial responses, and 147 partial responses). Serious adverse reactions were reported in 65.4% of patients treated with elotuzumab vs 56.5% patients treated on the control arm. The most frequent serious adverse reactions in the elotuzumab arm compared to the control arm were: pneumonia (15.4% vs. 11%), pyrexia (6.9% vs. 4.7%), respiratory tract infection (3.1% vs. 1.3%), anemia (2.8% vs. 1.9%), pulmonary embolism (3.1% vs. 2.5%), and acute renal failure (2.5% vs. 1.9%). (Lonial, 2015)
2018 Update
A literature search conducted through April 2018 did not reveal any new information that would prompt a change in the coverage statement.
Elotuzumab was evaluated in a proof-of-concept, open-label phase 2 study in which 150 patients were randomly assigned to receive either elotuzumab with bortezomib and dexamethasone (EBd) or bortezomib and dexamethasone (Bd). Patients were aged 18 years or older with a confirmed diagnosis of multiple myeloma and had documented progression after 1 to 3 prior lines of therapy. The study met its primary endpoint of PFS with a 28% reduction in the risk of progression or death with EBd compared with Bd. Median PFS was 9.7 months with EBd vs 6.9 months with Bd. The 1 year PFS rate was 39% with EBd vs 33% with Bd. Overall response rate for the elotuzumab group was 66% for the EBd vs 63% for the Bd group. Adverse event reporting was similar in both arms of the study. For the EBd group, AEs were reported at 100% while the BD group reported 96% AEs. The most common grade 3 or higher AEs were infections and thrombocytopenia. Thrombocytopenia occurred less in the EBd group (9%) than the Bd group (17%). (Jakubowiak, 2016)
The safety and efficacy of elotuzumab in combination with lenalidomide and dexamethasone were evaluated in a randomized, open-label trial in patients with multiple myeloma who had received one to three prior therapies and had documented progression following their most recent therapy. A total of 646 patients were randomized in a 1:1 ratio to receive either elotuzumab in combination with lenalidomide and low-dose dexamethasone or lenalidomide and low-dose dexamethasone. The median PFS for the elotuzumab group was 19.4 months while the standard treatment group PFS was 14.9 months. ORR was 78.5% (14 complete responses, 91 very good partial responses, and 147 partial responses). Serious adverse reactions were reported in 65.4% of patients treated with elotuzumab vs 56.5% patients treated on the control arm. The most frequent serious adverse reactions in the elotuzumab arm compared to the control arm were: pneumonia (15.4% vs. 11%), pyrexia (6.9% vs. 4.7%), respiratory tract infection (3.1% vs. 1.3%), anemia (2.8% vs. 1.9%), pulmonary embolism (3.1% vs. 2.5%), and acute renal failure (2.5% vs. 1.9%). (Lonial, 2015)
The immunostimulatory monoclonal antibody elotuzumab plus lenalidomide and dexamethasone has been shown to be effective in patients with relapsed or refractory multiple myeloma. The immunomodulatory agent pomalidomide plus dexamethasone has been shown to be effective in patients with multiple myeloma that is refractory to lenalidomide and a proteasome inhibitor. Patients with multiple myeloma that was refractory or relapsed and refractory to lenalidomide and a proteasome inhibitor were randomly assigned to receive elotuzumab plus pomalidomide and dexamethasone (elotuzumab group) or pomalidomide and dexamethasone alone (control group). The primary end point was investigator-assessed progression-free survival.
A total of 117 patients were randomly assigned to the elotuzumab group (60 patients) or the control group (57 patients). After a minimum follow-up period of 9.1 months, the median progression-free survival was 10.3 months in the elotuzumab group and 4.7 months in the control group. The hazard ratio for disease progression or death in the elotuzumab group as compared with the control group was 0.54 (95% confidence interval [CI], 0.34 to 0.86; P=0.008). The overall response rate was 53% in the elotuzumab group as compared with 26% in the control group (odds ratio, 3.25; 95% CI, 1.49 to 7.11). The most common grade 3 or 4 adverse events were neutropenia (13% in the elotuzumab group vs. 27% in the control group), anemia (10% vs. 20%), and hyperglycemia (8% vs. 7%). A total of 65% of the patients in each group had infections. Infusion reactions occurred in 3 patients (5%) in the elotuzumab group. Among patients with multiple myeloma in whom treatment with lenalidomide and a proteasome inhibitor had failed, the risk of progression or death was significantly lower among those who received elotuzumab plus pomalidomide and dexamethasone than among those who received pomalidomide plus dexamethasone alone.
2019 Update
A literature search conducted through March 2019 did not reveal any new information that would prompt a change in the coverage statement.
2020 Update
A literature search conducted through January 2020 did not reveal any new information that would prompt a change in the coverage statement.
2021 Update
Annual policy review completed with a literature search using the MEDLINE database through April 2021. No new literature was identified that would prompt a change in the coverage statement.
2022 Update
Annual policy review completed with a literature search using the MEDLINE database through April 2022. No new literature was identified that would prompt a change in the coverage statement.
2023 Update
In the phase II ELOQUENT-3 trial (ClinicalTrials.gov identifier: NCT02654132), elotuzumab combined with pomalidomide/dexamethasone (EPd) significantly improved progression-free survival (PFS) versus pomalidomide/dexamethasone (Pd) in patients with relapsed/refractory multiple myeloma (RRMM) previously treated with lenalidomide and a proteasome inhibitor (PI). Here, we present the final overall survival (OS) results.
Patients with RRMM who had received ≥ 2 prior lines of therapy, with disease refractory to last therapy and either refractory or relapsed and refractory to lenalidomide and a PI were randomly assigned (1:1) to receive EPd or Pd. The primary end point was PFS per investigator assessment. ORR and OS were secondary end points planned to be tested hierarchically.
A total of 117 patients were randomly assigned to EPd (n = 60) and Pd (n = 57). Among treated patients (EPd 60, Pd 55), there were 37 (61.7%) deaths in the EPd group and 41 (74.5%) in the Pd group, most commonly because of disease progression (EPd 41.7%, Pd 49.1%). Median (95% CI) OS was significantly improved with EPd (29.8 [22.9 to 45.7] months) versus Pd (17.4 [13.8 to 27.7] months), with a hazard ratio of 0.59 (95% CI, 0.37 to 0.93; P = .0217). OS benefit with EPd was observed in most patient subgroups. The safety profile of EPd was consistent with prior reports with no new safety signals detected.
EPd demonstrated a statistically significant improvement in OS versus Pd in patients with RRMM previously treated with lenalidomide and a PI who had disease refractory to last therapy. In this setting, ELOQUENT-3 is the first randomized study of a triplet regimen incorporating a monoclonal antibody and Pd to improve both PFS and OS significantly. (Dimopoulos MA, Dytfeld D, Grosicki S, 2023)
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| References: |
Bristol-Myers Squibb Company(2015) Empliciti® [package insert] Bristol-Myers Squibb Company.; revised 11/2018 Bristol-Myers Squibb Company(2015) Empliciti® [package insert]. Princeton, NJ: Bristol-Myers Squibb Company.; 2015 Dimopoulos MA, Dytfeld D, Grosicki S, Moreau P, Takezako N, Hori M, Leleu X, LeBlanc R, Suzuki K, Raab MS, Richardson PG, Popa McKiver M, Jou YM, Yao D, Das P, San-Miguel J.(2023) Elotuzumab Plus Pomalidomide and Dexamethasone for Relapsed/Refractory Multiple Myeloma: Final Overall Survival Analysis From the Randomized Phase II ELOQUENT-3 Trial. J Clin Oncol. 2023 Jan 20;41(3):568-578. doi: 10.1200/JCO.21.02815. Epub 2022 Aug 12. PMID: 35960908; PMCID: PMC9870233. Dimopoulos MA1, Dytfeld D1, Grosicki S1, Moreau P1, Takezako N1, Hori M1, Leleu X1, LeBlanc R1, Suzuki K1, Raab MS1, Richardson PG1, Popa McKiver M1, Jou YM1, Shelat SG1, Robbins M1, Rafferty B1, San-Miguel J1.(2018) Elotuzumab plus Pomalidomide and Dexamethasone for Multiple Myeloma N Engl J Med. 2018 Nov 8;379(19):1811-1822. doi: 10.1056/NEJMoa1805762. Elsevier.(2017) Elotuzumab [Internet]. Tampa (FL): Elsevier. c2017- [cited 2017 March 23]. Available from: http://www.clinicalpharmacology.com Jakubowiak A, Offidini M, Peqourie B, et al.(2016) Randomized phase 2 study: elotuzumab plus bortezomib/dexamethasone vs bortezomib/dexamethasone for relapsed/refractory MM. Blood 2016 June 9; 127(23): 2833–2840. Lonial, et al.(2015) Elotuzumab Therapy for Relapsed or Refractory Multiple Myeloma. N Engl J Med 2015; 373:621-631 National Comprehensive Cancer Network (NCCN)(2023) National Comprehensive Cancer Network, Inc. 2023 Practice Guidelines in Oncology—Multiple Myeloma v.3.2023. Available at https://www.nccn.org. Accessed April 12, 2023. NCCN(2017) NCCN Compendia. https://www.nccn.org/professionals/drug_compendium/MatrixGenerator/Matrix.aspx?AID=5. Accessed March 23, 2017. |
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Group specific policy will supersede this policy when applicable. This policy does not apply to the Wal-Mart Associates Group Health Plan participants or to the Tyson Group Health Plan participants.
CPT Codes Copyright © 2024 American Medical Association. |
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