FDA Approves Bristol-Myers Squibb's Empliciti Combo

Bristol-Myers Squibb Company announced that the FDA approved Empliciti (elotuzumab) injection for intravenous use in combination with pomalidomide and dexamethasone (EPd) for the treatment of adult patients with multiple myeloma who have received at least two prior therapies, including lenalidomide and a proteasome inhibitor.¹

In Eloquent-3, a randomized, open-label, Phase 2 trial, EPd demonstrated benefit in patients with relapsed or refractory multiple myeloma, doubling both median progression-free survival (PFS) and overall response rate (ORR) versus pomalidomide and dexamethasone (Pd).¹

“Empliciti plus pomalidomide and dexamethasone has been proven to extend the time that certain patients live without disease progression, giving health care professionals an effective new tool to tackle this relentless cancer,”^1,2 said Joseph E. Eid, M.D., senior vice president and head of Medical, Bristol-Myers Squibb. “Today’s approval reinforces the importance of Immuno-Oncology in blood cancers and expands the role of Empliciti to address the needs of relapsed or refractory multiple myeloma patients.”

Empliciti with pomalidomide and dexamethasone is associated with Warnings and Precautions related to: infusion reactions, infections, secondary primary malignancies, hepatotoxicity, interference with determination of complete response, pregnancy/females and males of reproductive potential and adverse reactions.¹ Please see the detailed important safety information below.

Following priority review by the FDA, EPd is the first triplet combination to be approved based on a randomized clinical trial using Pd as a comparator.^3,4 Results from the trial include:

Progression-free survival (primary endpoint, investigator-assessed):^1,3 EPd reduced the risk of disease progression by 46 percent, demonstrating a median PFS of 10.25 months (95 percent CI: 5.59 to non-estimable [NE]) vs. 4.67 months (95 percent CI: 2.83 to 7.16) for Pd alone after a minimum follow-up of 9.1 months.¹
Overall response rate (secondary endpoint, investigator-assessed):^1,3 Response rates doubled in patients receiving EPd (53.3 percent; n=32/60 [95 percent CI: 40.0 to 66.3]) compared with patients receiving Pd alone (26.3 percent; n=15/57 [95 percent CI: 15.5 to 39.7]; p=0.0029), with very good partial responses or better seen in 20 percent of EPd-treated patients (n=12) and 8.8 percent of Pd-treated patients (n=5).¹
Safety: Serious adverse reactions were reported in 22 percent of patients treated with EPd and in 15 percent of patients treated with Pd.¹Discontinuation of any component of the treatment regimen due to adverse reactions occurred in 5.0 percent of patients in the EPd arm, compared to 1.8 percent of patients in the control arm.¹

“Despite remarkable recent innovations with novel therapies for the treatment of multiple myeloma, many patients still face poor outcomes, and particularly in the relapsed and relapsed, refractory setting,”⁵said Paul Richardson, M.D., clinical program leader and director of clinical research of the Jerome Lipper Multiple Myeloma Center at Dana-Farber Cancer Institute. “This new regimen of elotuzumab combined with pomalidomide and dexamethasone not only extended the time to disease progression versus a standard of care but also doubled the response rate in some patients whose prior treatments had failed them.^1,6Thus to be able to offer an alternative with a meaningful clinical benefit is an important and significant milestone for our patients.”^1,4

Approximately 31,000 people in the United States will be diagnosed with multiple myeloma this year.⁷A common characteristic for many patients is that they experience multiple relapses, which means that the cancer returns after a period of remission.^8,9

“Relapse can be overwhelming and extremely challenging for multiple myeloma patients, particularly after they have already tried several therapies,”¹⁰ said Paul Giusti, president and chief executive officer of the Multiple Myeloma Research Foundation. “Empliciti, in combination with pomalidomide and dexamethasone, is an exciting new option for patients with relapsed or refractory myeloma.”

Bristol-Myers Squibb and AbbVie are co-developing Empliciti, with Bristol-Myers Squibb solely responsible for commercial activities.

About Eloquent-3

Eloquent-3 was a randomized, open-label Phase 2 study evaluating the addition of Empliciti to pomalidomide and dexamethasone versus pomalidomide and dexamethasone in 117 patients with multiple myeloma who received two or more prior therapies and were either refractory or relapsed and refractory to lenalidomide and a proteasome inhibitor.^1,3,4 Patients were randomized 1:1 to receive either EPd (n=60) or Pd (n=57) in 28-day cycles until disease progression or unacceptable toxicity.¹ The approved dose of Empliciti,when used in combination with pomalidomide and dexamethasone, is 10 mg/kg administered intravenously every week for the first two 28-day cycles, followed by 20 mg/kg every four weeks until disease progression or unacceptable toxicity.¹

The primary efficacy outcome measure of the trial was PFS as determined by the investigator.^1,3 The secondary efficacy outcome measure of ORR included complete, stringent-complete, very good partial and partial response rates as determined by investigator assessment, based on the International Myeloma Working Group criteria.^1,3 Data from the Eloquent-3 trial were presented at the 23rd Congress of the European Hematology Association in June 2018.⁴

References

Empliciti Prescribing Information. Empliciti U.S. Product Information. Last Updated: November 2018. Princeton, NJ: Bristol-Myers Squibb Company.
Ravi P, Kumar S, Cerhan J, et al. Defining cure in multiple myeloma: a comparative study of outcomes of young individuals with myeloma and curable hematologic malignancies. Blood Cancer J. 2018;8-26.
ClinicalTrials.gov. An Investigational Immuno-Therapy Trial of Pomalidomide and Low-Dose Dexamethasone With or Without Elotuzumab to Treat Refractory and Relapsed and Refractory Multiple Myeloma (ELOQUENT-3). https://clinicaltrials.gov/ct2/show/NCT02654132?term=NCT02654132&rank=1. Accessed September 25, 2018.
Dimopoulos M, Dytfeld D, Grosicki S, et al. Elotuzumab plus Pomalidomide/Dexamethasone (EPD) VS PD for the Treatment of Relapsed/Refractory Multiple Myeloma (RRMM): Results from the Phase 2, Randomized Open-Label ELOQUENT-3 Study. (Slides from Oral Presentation) Presentation: The 23^rd Congress of The European Hematology Association; June 2018; Stockholm, Sweden.
Kurtin S. Relapsed or relapse/refractory multiple myeloma. J Adv Pract Oncol. 2013;4.
NCCN Clinical Practice Guidelines in Oncology. Multiple Myeloma. 2018.
Siegel RL, Miller KD, Jemal A. Cancer statistics, 2018. CA Cancer J Clin. 2018;68(1):7-30.
Rajkumar SV. Multiple myeloma: 2018 update on diagnosis, risk-stratification and management. Am J Hematol. 2016 Jul;91(7):719-34.
National Cancer Institute. NCI Dictionary of Cancer Terms: Relapse. https://www.cancer.gov/publications/dictionaries/cancer-terms/def/relapse. Accessed September 24, 2018.
Hulin C, Hansen T, Heron L, et al. Living with the burden of relapse in multiple myeloma from the patient and physician perspective. Leuk Res. 2017;59:75-84.