Bristol-Myers Squibb Presents Updated Efficacy Data from Phase 2 Trial of Empliciti (elotuzumab) Plus Pomalidomide and Dexamethasone in Patients with Relapsed or Refractory Multiple Myeloma (RRMM)
June 14, 2019
In a descriptive analysis, addition of Empliciti to
pomalidomide and dexamethasone reduced risk of death by 46% among
patients with RRMM
Empliciti-based combination showed improvements across efficacy
endpoints, including continued progression-free survival benefit at 18
months
PRINCETON, N.J.–(BUSINESS WIRE)–$BMY #BMS—Bristol-Myers
Squibb Company (NYSE: BMY) today announced the presentation of
updated data from ELOQUENT-3, the international randomized Phase 2 study
evaluating Empliciti (elotuzumab) plus pomalidomide and
dexamethasone (EPd) versus pomalidomide and dexamethasone (Pd) alone in
patients with relapsed or refractory multiple myeloma (RRMM). In a
non-prespecified analysis conducted to provide a descriptive assessment
of overall survival (OS) after extended follow-up of at least 18.3
months, patients treated with EPd continued to experience sustained and
clinically relevant OS and progression-free survival (PFS) benefits
compared with patients treated with Pd.
Treatment with EPd was associated with a 46% reduction in risk of death
[Hazard Ratio (HR) 0.54; 95% Confidence Interval (CI): 0.30 to 0.96]
versus treatment with Pd alone. At 18 months, rates of OS, a secondary
endpoint, were 68% for patients treated with EPd compared to 49% for
patients treated with Pd. Median OS was not reached with EPd [95% CI:
24.9 months, Not Estimable (NE)] at the time of analysis and was 17.4
months (95% CI: 13.8, NE) among patients receiving Pd. Eighteen-month
PFS rates were 34% among patients randomized to EPd compared to 11%
among patients randomized to Pd. Safety results for EPd were consistent
with the primary analysis and with prior findings for Empliciti and
pomalidomide regimens.
These data will be presented at the 24th Congress of the
European Hematology Association (EHA) in Amsterdam in a poster display
(Abstract #PS1370) on Saturday, June 15 from 5:30-7 PM CEST.
“Multiple myeloma is a disease characterized by relapse, making it all
the more important to have effective options available for patients
after initial treatments. With 18 months of follow-up from the
ELOQUENT-3 trial, we continue to see meaningful improvements across key
endpoints with EPd versus Pd alone, including a positive trend in
overall survival,” said Meletios A. Dimopoulos, M.D., professor and
chairman of the Department of Clinical Therapeutics at Kapodistrian
University of Athens School of Medicine. “These data point to the
potential for this combination to become a new standard of care for
patients with multiple myeloma that returned after or did not respond to
prior therapies, including lenalidomide and a proteasome inhibitor.”
“The extended follow-up results from ELOQUENT-3 reinforce the EPd
combination’s sustained efficacy and favorable safety profile in
patients with relapsed or refractory multiple myeloma,” said Fouad
Namouni, M.D., head, Oncology Development, Bristol-Myers Squibb. “These
data, along with our overall presence at EHA, underscore our commitment
to leading innovative research in hematology and developing therapies
that can improve long-term survival for patients with different types of
blood cancer.”
Data from the primary analysis of ELOQUENT-3 were published in the New
England Journal of Medicine in November 2018 and supported the
approval of EPd by the U.S. Food and Drug Administration for the
treatment of adult patients with RRMM who have received at least two
prior therapies, including lenalidomide and a proteasome inhibitor.
Bristol-Myers Squibb and AbbVie are co-developing Empliciti, with
Bristol-Myers Squibb solely responsible for commercial activities.
About ELOQUENT-3
The Phase 2 ELOQUENT-3 trial randomized 117 patients with RRMM who
received two or more prior therapies and were either refractory or
relapsed and refractory to lenalidomide and a proteasome inhibitor.
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.
Patients in both the EPd and Pd arms received 4 mg of pomalidomide for
days 1-21 of each cycle, and the weekly equivalent of 40 mg or 20 mg
dexamethasone for patients ≤75 years or >75 years, respectively. In the
EPd arm, Empliciti was administered intravenously at the dose of
10 mg/kg weekly for the first 2 cycles and 20 mg/kg every four weeks
starting from cycle 3. The primary endpoint of the study was
investigator-assessed PFS.
In the 18-month follow-up analysis, adverse events (AEs) were comparable
between treatment arms and consistent with the primary analysis. The
most common grade 3-4 AEs were infections (22% among patients receiving
EPd, 24% among patients receiving Pd), neutropenia (13%, 29%), anemia
(10%, 22%), thrombocytopenia (10%, 7%) and hyperglycemia (8%, 11%).
Grade 5 all-cause AEs occurred in seven patients (12%) who received EPd
and nine patients (16%) who received Pd.
Bristol-Myers Squibb: Advancing Oncology
Research
At Bristol-Myers Squibb, patients are at the center of everything we do.
The focus of our research is to increase quality, long-term survival for
patients and make cure a possibility. Through a unique multidisciplinary
approach powered by translational science, we harness our deep
scientific experience in oncology and Immuno-Oncology (I-O) research to
identify novel treatments tailored to individual patient needs. Our
researchers are developing a diverse, purposefully built pipeline
designed to target different immune system pathways and address the
complex and specific interactions between the tumor, its
microenvironment and the immune system. We source innovation internally,
and in collaboration with academia, government, advocacy groups and
biotechnology companies, to help make the promise of transformational
medicines, like I-O, a reality for patients.
About Empliciti
Empliciti is an immunostimulatory antibody that specifically
targets Signaling Lymphocyte Activation Molecule Family member 7
(SLAMF7), a cell-surface glycoprotein. SLAMF7 is expressed on myeloma
cells independent of cytogenetic abnormalities. SLAMF7 also is expressed
on Natural Killer cells, plasma cells and at lower levels on specific
immune cell subsets of differentiated cells within the hematopoietic
lineage.
Empliciti has a dual mechanism of action. It directly activates
the immune system through Natural Killer cells via the SLAMF7 pathway. Empliciti also
targets SLAMF7 on myeloma cells, tagging these malignant cells for
Natural Killer cell-mediated destruction via antibody-dependent cellular
toxicity.
Empliciti was initially approved by the FDA in 2015 in
combination with lenalidomide and dexamethasone for the treatment of
patients with multiple myeloma who have received one to three prior
therapies.
U.S. FDA-APPROVED INDICATIONS FOR EMPLICITI®
EMPLICITI® (elotuzumab) is indicated in combination with
lenalidomide and dexamethasone for the treatment of adult patients with
multiple myeloma who have received one to three prior therapies.
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.
IMPORTANT SAFETY INFORMATION
Infusion Reactions
Infusion reactions were reported in 10% of patients treated with
EMPLICITI in the ELOQUENT-2 trial [EMPLICITI + lenalidomide +
dexamethasone (ERd) vs lenalidomide + dexamethasone (Rd)] and 3.3% in
the ELOQUENT-3 trial [EMPLICITI + pomalidomide + dexamethasone (EPd) vs
pomalidomide + dexamethasone (Pd)].
In the ELOQUENT-2 trial, all infusion reactions were Grade 3 or lower,
with Grade 3 infusion reactions occurring in 1% of patients. The most
common symptoms included fever, chills, and hypertension. Bradycardia
and hypotension also developed during infusions. In the trial, 5% of
patients required interruption of the administration of EMPLICITI for a
median of 25 minutes due to infusion reactions, and 1% of patients
discontinued due to infusion reactions. Of the patients who experienced
an infusion reaction, 70% (23/33) had them during the first dose.
In the ELOQUENT-3 trial, 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-2 trial (N=635), infections were reported in 81% of
patients in the ERd arm and 74% in the Rd arm. Grade 3-4 infections were
28% (ERd) and 24% (Rd). Discontinuations due to infections were 3.5%
(ERd) and 4.1% (Rd). Fatal infections were 2.5% (ERd) and 2.2% (Rd).
Opportunistic infections were reported in 22% (ERd) and 13% (Rd). Fungal
infections were 10% (ERd) and 5% (Rd). Herpes zoster was 14% (ERd) and
7% (Rd).
In the ELOQUENT-3 trial (N=115), infections were reported in 65% of
patients in both the EPd arm and the Pd arm. Grade 3-4 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-2 trial (N=635), invasive second primary malignancies
(SPM) were 9% (ERd) and 6% (Rd). The rate of hematologic malignancies
was the same between ERd and Rd treatment arms (1.6%). Solid tumors were
reported in 3.5% (ERd) and 2.2% (Rd). Skin cancer was reported in 4.4%
(ERd) and 2.8% (Rd).
In the ELOQUENT-3 trial (N=115), invasive SPMs 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% (ERd) vs 0.6% (Rd). 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 birth defects and miscarriage.
There is a risk of fetal harm, including severe life-threatening human
birth defects, associated with lenalidomide and pomalidomide, and they
are contraindicated for use in pregnancy. Refer to the respective
product 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
ELOQUENT-2 trial:
-
Serious adverse reactions were 65% (ERd) and 57% (Rd). The most
frequent serious adverse reactions in the ERd arm compared to the Rd
arm were: pneumonia (15%, 11%), pyrexia (7%, 5%), respiratory tract
infection (3.1%, 1.3%), anemia (2.8%, 1.9%), pulmonary embolism (3.1%,
2.5%), and acute renal failure (2.5%, 1.9%). -
The most common adverse reactions in ERd and Rd, respectively (≥20%)
were fatigue (62%, 52%), diarrhea (47%, 36%), pyrexia (37%, 25%),
constipation (36%, 27%), cough (34%, 19%), peripheral neuropathy (27%,
21%), nasopharyngitis (25%, 19%), upper respiratory tract infection
(23%, 17%), decreased appetite (21%, 13%), and pneumonia (20%, 14%).
ELOQUENT-3 trial:
-
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.
About Bristol-Myers Squibb
Bristol-Myers Squibb is a global biopharmaceutical company whose mission
is to discover, develop and deliver innovative medicines that help
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About AbbVie in Oncology
At AbbVie, we strive to discover and develop medicines that deliver
transformational improvements in cancer treatment by uniquely combining
our deep knowledge in core areas of biology with cutting-edge
technologies, and by working together with our partners – scientists,
clinical experts, industry peers, advocates, and patients. We remain
focused on delivering these transformative advances in treatment across
some of the most debilitating and widespread cancers. We are also
committed to exploring solutions to help patients obtain access to our
cancer medicines. With the acquisitions of Pharmacyclics in 2015 and
Stemcentrx in 2016, our research and development efforts, and through
collaborations, AbbVie’s oncology portfolio now consists of marketed
medicines and a pipeline containing multiple new molecules being
evaluated worldwide in more than 200 clinical trials and more than 20
different tumor types. For more information, please visit https://www.abbvie.com/our-science/therapeutic-focus-areas/oncology.html.
Bristol-Myers Squibb Forward-Looking Statement
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meaning of the Private Securities Litigation Reform Act of 1995
regarding, among other things, the research, development and
commercialization of pharmaceutical products. All statements that are
not statements of historical facts are, or may be deemed to be,
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regulatory approval for the additional indication described in this
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