Combination therapy demonstrated a sustained reduction in risk of
progression/death of 29% and relative improvement of 50% in
progression-free survival rate of ELd (21%) compared to Ld alone (14%)
The extended follow-up data is the longest of an Immuno-Oncology
agent in relapsed/refractory multiple myeloma
The data showed a safety profile consistent with prior findings
PRINCETON, N.J.--(BUSINESS WIRE)--
Bristol-Myers
Squibb Company (NYSE:BMY) presented four-year follow-up data from
the Phase 3 ELOQUENT-2 study in which Empliciti (elotuzumab) plus
lenalidomide/dexamethasone (ELd) continued to demonstrate efficacy in
patients with relapsed/refractory multiple myeloma (RRMM), compared to
patients treated with lenalidomide/dexamethasone (Ld) alone. The data
also showed a safety profile consistent with prior findings. The results
were presented in an oral session today during the 22nd
Congress of the European Hematology Association in Madrid, Spain and
offer the longest follow-up efficacy and safety data of an
Immuno-Oncology agent.
ELd therapy maintained a reduction in the risk of disease progression or
death of 29% (HR 0.71; 95% CI: 0.59 to 0.86). At four-years, ELd therapy
continued to demonstrate a clinically meaningful and sustained relative
improvement of 50% in progression-free survival (PFS) rate, 21% (95% CI:
16.6, 22.3), compared to Ld therapy, 14% (95% CI: 12.1,17.3). PFS
benefits seen in patients receiving ELd therapy were consistent across
certain patient subsets and sustained through two-year, three-year and
four-year follow-up. Patients with high risk* (n=60 ELd, n=66
Ld) showed relative risk reduction of 36% (HR=0.64; 95% CI :0.43 to
0.97) and more than doubling of median PFS (15.2 ELd vs 7.4 Ld) with ELd
in comparison to Ld.
Patients receiving ELd therapy demonstrated an overall response rate
(ORR) of 79% (253/321 patients, 95% CI: 73.9 to 83.2), compared to 66%
(214/325 patients, 95% CI: 60.4 to 71.0) among patients receiving Ld
therapy alone. While OS was not pre-specified for the four-year
follow-up, Empliciti in combination with Ld data also
demonstrated a median overall survival (OS) benefit of 48 months (95%
CI: 40.3 to 54.4) in favor of ELd versus a median OS of 40 months for Ld
(95% CI: 33.3 to 45.4), a difference of 22% (HR 0.78; 95% CI: 0.63 to
0.96). Early separation of OS Kaplan Meier survival curves was
maintained over time in favor of ELd versus Ld.
“These extended four-year follow-up data demonstrated that adding Empliciti
to Ld yielded clinically relevant improvements and reductions in the
risk of disease progression or death for patients with
relapsed/refractory multiple myeloma, compared to Ld alone,” Meletios A.
Dimopoulos, M.D., ELOQUENT-2 investigator and professor and chairman of
the Department of Clinical Therapeutics at the National and Kapodistrian
University of Athens School of Medicine. “This data at four-year
follow-up is particularly notable as it suggests the ability of this
Immuno-Oncology agent to build a sustainable immune response in some
patients with advanced multiple myeloma.”
The rates of adverse events (AE) were similar between patients receiving
ELd or Ld therapy and consistent with those reported at two- and
three-year follow-up. The most common AEs (all grades) in ELd and Ld,
respectively, were diarrhea (49%, 38%), fatigue (48%, 41%), anemia (43%,
38%), pyrexia (40%, 25%), constipation (36%, 28%), neutropenia (35%,
43%), cough (34%, 19%), back pain (31%, 29%), and muscle spasm (31%,
26%).
“The long-term efficacy data for Empliciti in patients with
advanced multiple myeloma shows the combination of this Immuno-Oncology
agent with standard lenalidomide/dexamethasone treatment can improve
patient outcomes,” said Jonathan Leith, Ph.D., hematology development
lead, Bristol-Myers Squibb. “These findings illustrate Bristol-Myers
Squibb’s commitment to exploring how Immuno-Oncology agents might best
help appropriate patients.”
About ELOQUENT-2
The ELOQUENT-2 trial randomized 646 patients with RRMM who had one to
three prior therapies to receive either ELd (321 patients) or Ld (325
patients) in 28-day cycles until their disease progressed, the
occurrence of unacceptable toxicity or they withdrew consent. In the ELd
arm, patients were administered 10 mg/kg by IV of elotuzumab for weeks
one and two of the 28-day cycle and then every other week, along with 25
mg of lenalidomide by mouth for days 1-21 of the cycle and the weekly
equivalent of 40 mg of dexamethasone by mouth. In the Ld arm, patients
were given 25 mg of lenalidomide by mouth for days 1-21 of the cycle and
the weekly equivalent of 40 mg of dexamethasone by mouth.
The occurrence of treatment-related Grade 3–4 AEs in 5% or more of
patients were generally comparable between the ELd and Ld groups:
vascular diseases (10% vs. 8%; mostly venous-related), second primary
malignancies (9% vs. 6%), and cardiac disorders (5% vs. 8%). ELd therapy
did have a slightly higher incidence of infection compared to Ld (33%
vs. 26%). ELd treatment also had higher overall rates than Ld of any
grade infection (84% vs. 75%) and second primary malignancies (17% vs.
11%). However, exposure to ELd was longer than to Ld, with a median
treatment cycle of 19 months (9 to 42) compared to 14 months (6 to 25),
respectively. While disease progression and infection were major causes
of deaths in both groups, fewer were reported with ELd (165) than with
Ld (186) treatment.
On November 30, 2015, the U.S. Food and Drug Administration (FDA)
approved Empliciti in combination with lenalidomide and
dexamethasone in patients with multiple myeloma who have received one to
three prior therapies. On May 11, 2016, the European Commission approved Empliciti
in combination with lenalidomide and dexamethasone in patients with
multiple myeloma who have received at least one prior therapy.
Bristol-Myers Squibb & Immuno-Oncology:
Advancing Oncology Research
At Bristol-Myers Squibb, patients are at the center of everything we do.
Our vision for the future of cancer care is focused on researching and
developing transformational Immuno-Oncology (I-O) medicines for
hard-to-treat cancers that could potentially improve outcomes for these
patients.
We are leading the scientific understanding of I-O through our extensive
portfolio of investigational compounds and approved agents. Our
differentiated clinical development program is studying broad patient
populations across more than 50 types of cancers with 14 clinical-stage
molecules designed to target different immune system pathways. Our deep
expertise and innovative clinical trial designs position us to advance
I-O/I-O, I-O/chemotherapy, I-O/targeted therapies and I-O/radiation
therapies across multiple tumors and potentially deliver the next wave
of therapies with a sense of urgency. We also continue to pioneer
research that will help facilitate a deeper understanding of the role of
immune biomarkers and how patients’ individual tumor biology can be used
as a guide for treatment decisions throughout their journey.
We understand making the promise of I-O a reality for the many patients
who may benefit from these therapies requires not only innovation on our
part but also close collaboration with leading experts in the field. Our
partnerships with academia, government, advocacy and biotech companies
support our collective goal of providing new treatment options to
advance the standards of clinical practice.
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.
Bristol-Myers Squibb and AbbVie are co-developing Empliciti, with
Bristol-Myers Squibb solely responsible for commercial activities.
U.S. FDA-APPROVED INDICATION FOR EMPLICITI ™
EMPLICITI™ (elotuzumab) is indicated in combination with lenalidomide
and dexamethasone for the treatment of patients with multiple myeloma
who have received one to three prior therapies.
IMPORTANT SAFETY INFORMATION
Infusion Reactions
-
EMPLICITI can cause infusion reactions. Common symptoms include 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. 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 infusing with EMPLICITI.
Infections
-
In a clinical trial of patients with multiple myeloma (N=635),
infections were reported in 81.4% of patients in the EMPLICITI with
lenalidomide/dexamethasone arm (ERd) and 74.4% in the
lenalidomide/dexamethasone arm (Rd). Grade 3-4 infections were 28%
(ERd) and 24.3% (Rd). Opportunistic infections were reported in 22%
(ERd) and 12.9% (Rd). Fungal infections were 9.7% (ERd) and 5.4% (Rd).
Herpes zoster was 13.5% (ERd) and 6.9% (Rd). Discontinuations due to
infections were 3.5% (ERd) and 4.1% (Rd). Fatal infections were 2.5%
(ERd) and 2.2% (Rd). Monitor patients for development of infections
and treat promptly.
Second Primary Malignancies
-
In a clinical trial of patients with multiple myeloma (N=635),
invasive second primary malignancies (SPM) were 9.1% (ERd) and 5.7%
(Rd). The rate of hematologic malignancies were 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).
Monitor patients for the development of SPMs.
Hepatotoxicity
-
Elevations in liver enzymes (AST/ALT greater than 3 times the upper
limit, total bilirubin greater than 2 times the upper limit, and
alkaline phosphatase less than 2 times the upper limit) consistent
with hepatotoxicity were 2.5% (ERd) and 0.6% (Rd). Two patients
experiencing hepatotoxicity discontinued treatment; however, 6 out of
8 patients had resolution and continued treatment. Monitor liver
enzymes periodically. Stop EMPLICITI upon Grade 3 or higher elevation
of liver enzymes. After return to baseline values, continuation of
treatment may be considered.
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 studies with EMPLICITI with pregnant women to inform any
drug associated risks.
-
There is a risk of fetal harm, including severe life-threatening human
birth defects associated with lenalidomide and it is contraindicated
for use in pregnancy. Refer to the lenalidomide 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
-
Infusion reactions were reported in approximately 10% of patients
treated with EMPLICITI with lenalidomide and dexamethasone. All
reports of infusion reaction were Grade 3 or lower. Grade 3 infusion
reactions occurred in 1% of patients.
-
Serious adverse reactions were 65.4% (ERd) and 56.5% (Rd). The most
frequent serious adverse reactions in the ERd arm compared to the Rd
arm were: pneumonia (15.4%, 11%), pyrexia (6.9%, 4.7%), 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 (61.6%, 51.7%), diarrhea (46.9%, 36.0%), pyrexia (37.4%,
24.6%), constipation (35.5%, 27.1%), cough (34.3%, 18.9%), peripheral
neuropathy (26.7%, 20.8%), nasopharyngitis (24.5%, 19.2%), upper
respiratory tract infection (22.6%, 17.4%), decreased appetite (20.8%,
12.6%), and pneumonia (20.1%, 14.2%).
Please see the full Prescribing Information for EMPLICITI.
About Bristol-Myers Squibb
Bristol-Myers Squibb is a global biopharmaceutical company whose mission
is to discover, develop and deliver innovative medicines that help
patients prevail over serious diseases. For more information about
Bristol-Myers Squibb, visit us at BMS.com
or follow us on LinkedIn,
Twitter,
YouTube
and Facebook.
Bristol-Myers Squibb Forward-Looking Statement
This press release contains "forward-looking statements" as that term
is defined in the Private Securities Litigation Reform Act of 1995
regarding the research, development and commercialization of
pharmaceutical products. Such forward-looking statements are based on
current expectations and involve inherent risks and uncertainties,
including factors that could delay, divert or change any of them, and
could cause actual outcomes and results to differ materially from
current expectations. No forward-looking statement can be guaranteed.
Forward-looking statements in this press release should be evaluated
together with the many uncertainties that affect Bristol-Myers Squibb's
business, particularly those identified in the cautionary factors
discussion in Bristol-Myers Squibb's Annual Report on Form 10-K for the
year ended December 31, 2016 in our Quarterly Reports on Form 10-Q and
our Current Reports on Form 8-K. Bristol-Myers Squibb undertakes no
obligation to publicly update any forward-looking statement, whether as
a result of new information, future events or otherwise.
*High risk = ISS stage II or III and t(4;14) or del(17p) abnormality
Standard risk = patients not meeting either the definition of high risk
or low risk, which is defined as ISS stage I or II and absence of
t(4;14), del(17p) and 1q21 abnormalities and age <55
View source version on businesswire.com: http://www.businesswire.com/news/home/20170624005005/en/
Source: Bristol-Myers Squibb Company