This article is intended for U.S. healthcare professionals only.

Descriptive Analysis from Phase 2 ELOQUENT-3 Trial Unveils Updated Data

Unplanned Overall Survival Results for EMPLICITI® (elotuzumab) Plus Pomalidomide and Dexamethasone

August 20, 2019

D

espite recent progress in the treatment of multiple myeloma, it remains a challenging disease to manage. This is especially the case in patients who relapse or do not respond to multiple lines of therapy.1 Oftentimes, these patients face diminished outcomes, including reduced overall survival (OS), particularly after failure of immunomodulatory therapies and proteasome inhibitors.2

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As research has continued, additional treatment options have emerged that may help address the unmet needs of patients with relapsed/refractory multiple myeloma.1 One such option is the combination of Empliciti, an immunotherapy, with pomalidomide and dexamethasone (EPd), which was approved by the U.S. Food & Drug Administration (FDA) in November 2018 for adult patients who have received at least two prior therapies, including lenalidomide and a proteasome inhibitor.3

With this approval, which was based on the randomized Phase 2 ELOQUENT-3 trial, EPd became the first FDA-approved relapsed/refractory triplet regimen with study results versus pomalidomide and dexamethasone (Pd).4,5  

Now, additional data from a non-prespecified descriptive analysis of ELOQUENT-3 are available. 6

“The approval of EPd represented an important step forward for appropriate patients with relapsed/refractory multiple myeloma, adding another treatment option in a setting where there is an ongoing need for more therapies,” said Awny Farajallah, M.D., head of U.S. Medical at Bristol-Myers Squibb. “As we see more data from the ELOQUENT-3 trial, we can continue to build on our understanding of the efficacy and safety of the EPd combination over time.”

Empliciti with pomalidomide and dexamethasone is associated with warnings & precautions related to infusions reactions, infections, secondary primary malignancies, hepatotoxicity, interference with determination of complete response, pregnancy/females and males of reproductive potential and adverse reactions. Please see the detailed Important Safety Information at the end of this article. 

Data presented at the 24th Congress of the European Hematology Association in Amsterdam, reflect a minimum of 18.3 months of follow-up and include an analysis exploring OS rates for EPd versus Pd alone.6

ELOQUENT-3 Primary Analysis 

In the ELOQUENT-3 trial, 117 patients who had received two or more prior therapies and were either refractory or relapsed and refractory to lenalidomide and a proteasome inhibitor were randomized to receive either EPd (n=60) or Pd (n=57) in 28-day cycles until disease progression or unacceptable toxicity.3

In the primary analysis after a minimum follow-up of 9.1 months, EPd doubled PFS and ORR compared to Pd.3

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Serious adverse reactions were reported in 22% of patients treated with EPd and in 15% of patients treated with Pd.3 The most frequent serious adverse reactions in the EPd arm compared to the Pd arm were pneumonia (13% vs 11%) and respiratory tract infection (7% vs 3.6%).3 The most common adverse reactions occurring in 20% or more of patients treated with EPd and Pd, respectively, were constipation (22% vs 11%) and hyperglycemia (20% vs 15%).3

The ELOQUENT-3 trial showed that treatment with EPd is associated with certain risks, including additional adverse reactions that can become serious or life threatening (see Important Safety Information below).

ELOQUENT-3 18-Month Descriptive OS Results

In the unplanned, descriptive analysis, EPd was associated with an OS rate of 68% at 18 months vs. 49% for Pd.6

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Safety results in the 18-month analysis were consistent with the primary analysis.6

“Last year, at EHA 2018, we presented results from the ELOQUENT-3 trial, showing a statistically significant benefit for EPd vs. Pd in certain patients with relapsed/refractory multiple myeloma. One year later, we now have more information about this combination,” said Dr. Farajallah. "We’re committed to continuing our research into EPd, as well as in multiple myeloma more broadly, with the ultimate goal of improving outcomes for these patients."

For more information about EPd, please visit https://www.Empliciti.com.

INDICATION

EMPLICITI® (elotuzumab) is indicated in combination with pomalidomide and dexamethasone for the treatment of adult patients with multiple myeloma who have received at least two prior therapies including lenalidomide and a proteasome inhibitor.

EMPLICITI is available for injection for intravenous use in 300 mg and 400 mg vials.

IMPORTANT SAFETY INFORMATION

Infusion Reactions

  • Infusion reactions were reported in 3.3% of patients treated with EMPLICITI in the ELOQUENT-3 trial [EMPLICITI + pomalidomide + dexamethasone (EPd) vs pomalidomide + dexamethasone (Pd)]. The only infusion reaction symptom was chest discomfort (2%), which was Grade 1. All the patients who experienced an infusion reaction had them during the first treatment cycle.
  •  If a Grade 2 or higher infusion reaction occurs, interrupt the EMPLICITI infusion and institute appropriate medical and supportive measures. If the infusion reaction recurs, stop the EMPLICITI infusion and do not restart it on that day. Severe infusion reactions may require permanent discontinuation of EMPLICITI therapy and emergency treatment.
  • Premedicate with dexamethasone, H1 blocker, H2 blocker, and acetaminophen prior to EMPLICITI infusion.

Infections

  •  In the ELOQUENT-3 trial (N=115), infections were reported in 65% of patients in both the EPd arm and the Pd arm. Grade 3 to 4 infections were reported in 13% (EPd) and 22% (Pd). Discontinuations due to infections were 7% (EPd) and 5% (Pd). Fatal infections were 5% (EPd) and 3.6% (Pd). Opportunistic infections were reported in 10% (EPd) and 9% (Pd). Herpes zoster was reported in 5% (EPd) and 1.8% (Pd).
  • Monitor patients for development of infections and treat promptly.

Second Primary Malignancies

  • In the ELOQUENT-3 trial (N=115), invasive second primary malignancies (SPM) were 0% (EPd) and 1.8% (Pd). Monitor patients for the development of SPMs.

Hepatotoxicity

  •  In the ELOQUENT-2 trial (N=635), AST/ALT >3X the upper limit, total bilirubin >2X the upper limit, and alkaline phosphatase <2X the upper limit were 2.5% (EMPLICITI arm) vs 0.6% (control arm). Of 8 patients experiencing hepatotoxicity, 2 patients discontinued treatment while 6 patients had resolution and continued. Monitor liver enzymes periodically. Stop EMPLICITI upon ≥Grade 3 elevation of liver enzymes. Continuation of treatment may be considered after return to baseline values.

Interference with Determination of Complete Response

EMPLICITI is a humanized IgG kappa monoclonal antibody that can be detected on both the serum protein electrophoresis and immunofixation assays used for the clinical monitoring of endogenous M-protein. This interference can impact the determination of complete response and possibly relapse from complete response in patients with IgG kappa myeloma protein.

Pregnancy/Females and Males of Reproductive Potential

  • There are no available data on EMPLICITI use in pregnant women to inform a drug-associated risk of major defects and miscarriage. 
  • There is a risk of fetal harm, including severe life-threatening human birth defects, associated with pomalidomide, and it is contraindicated for use in pregnancy. Refer to the pomalidomide full prescribing information for requirements regarding contraception and the prohibitions against blood and/or sperm donation due to presence and transmission in blood and/or semen and for additional information.

Adverse Reactions

  • Serious adverse reactions were 22% (EPd) and 15% (Pd). The most frequent serious adverse reactions in the EPd arm compared to the Pd arm were: pneumonia (13%, 11%) and respiratory tract infection (7%, 3.6%).
  • The most common adverse reactions in EPd arm (≥20% EPd) and Pd, respectively, were constipation (22%, 11%) and hyperglycemia (20%, 15%).

Please see the full  Prescribing Information for Empliciti.

EMPLICITI is a registered trademark of Bristol-Myers Squibb Company.
© 2019 Bristol-Myers Squibb Company. All rights reserved.
689US1902167-01-01 07/19
References:
1.  Kurtin S. Relapsed or Relapsed/Refractory Multiple Myeloma. J Adv Pract Oncol. 2013;4(6),5-14.
2.  Kumar SK, Dimopoulos MA, Kastritis E, et al. Natural history of relapsed myeloma, refractory to immunomodulatory drugs and proteasome inhibitors: a multicenter IMWG study. Nature. 2017;31(11),2443-2448.
3.  Empliciti Prescribing Information. Empliciti U.S. Product Information. Last updated: November 2018. Princeton, NJ: Bristol-Myers Squibb Company. 
4.  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). Food and Drug Administration website https://clinicaltrials.gov/ct2/show/NCT02654132?term=NCT02654132&rank=1. Updated June 3, 2019. Accessed July 22, 2019.
5.  Dimopoulos M, Dytfeld D, Grosicki S, et al. Elotuzumab Plus Pomalidomide/Dexamethasone (EPd) vs Pd for Treatment of Relapsed/Refractory Multiple Myeloma: Results From the Phase 2, Randomized Open-Label ELOQUENT-3 Study. Poster presented at: 23rd European Hematology Association (EHA) Annual Meeting; June 14-17, 2018; Stockholm, Sweden. 
6.  Dimopoulos M, Dytfeld D, Grosicki S, et al. Elotuzumab Plus Pomalidomide and Dexamethasone for Relapsed/Refractory Multiple Myeloma: Efficacy Results After Additional Follow-Up of the Phase 2, Randomized ELOQUENT-3 Study. Poster presented at: 24th European Hematology Association (EHA) Annual Meeting; June 13-16, 2019; Amsterdam, The Netherlands.