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
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
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version on businesswire.com: http://www.businesswire.com/news/home/20170624005005/en/
Bristol-Myers Squibb CompanyMedia:Audrey Abernathy, cell:
919-605-4521audrey.abernathy@bms.comorInvestor:Bill
Szablewski, 609-252-5894william.szablewski@bms.comorTim Power,
609-252-7509timothy.power@bms.com
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