Extended follow-up and overall survival update
from pivotal ELOQUENT-2 trial, evaluating elotuzumab as combination
therapy in relapsed or refractory multiple myeloma, to be
presented
New extended follow-up data from Checkmate
-039, evaluating Opdivo (nivolumab) in Hodgkin lymphoma, to be
presented
Chronic myeloid leukemia health economic data
to be presented during oral presentation
Bristol-Myers Squibb Company (NYSE:BMY) today announced the
presentation of clinical research from its hematology portfolio at
the 57th Annual Meeting & Exposition of the American Society of
Hematology (ASH) in Orlando, FL, December 5-8. Bristol-Myers Squibb
will present data for elotuzumab, an investigational
immunostimulatory antibody, in patients with relapsed or refractory
(R/R) multiple myeloma (MM); for Opdivo (nivolumab) for an
investigational use in patients with R/R classical Hodgkin lymphoma
(cHL); and for Sprycel (dasatinib) in chronic myeloid leukemia
(CML).
Data to be presented during oral presentations include:
- ELOQUENT-2: Extended follow-up
and overall survival data from a randomized, open-label, Phase 3
study [Abstract #28] comparing elotuzumab in combination with
lenalidomide and dexamethasone versus lenalidomide and
dexamethasone alone in patients with R/R MM will be presented on
Saturday, December 5, 8:15 a.m. EST. Results from the primary
analysis of the ELOQUENT-2 study were published in The New England
Journal of Medicine on June 2, 2015.
- Study CA204-009: A Phase 2,
open-label study [Abstract #510] comparing elotuzumab in
combination with bortezomib (a proteasome inhibitor) and
dexamethasone versus bortezomib and dexamethasone alone in patients
with R/R MM will be presented on Monday, December 7, 8:15 a.m.
EST.
- Checkmate -039: New extended
follow-up on the Phase 1 study [Abstract #583] of Opdivo for an
investigational use in patients with R/R cHL will be presented
December 7, 10:30 a.m. EST. Earlier results from the cHL cohort
enrolled in Checkmate -039 were published in The New England
Journal of Medicine on December 6, 2014.
- Study CA180-590: A study
[Abstract #876] on the economic burden of adverse events associated
with tyrosine kinase inhibitors in patients with CML will be
presented on December 7, 5:45 p.m. EST.
“We are proud to present data across our rapidly expanding
hematology portfolio that validates our leading Immuno-Oncology
approach and leverages our deep scientific expertise with the goal
of improving outcomes for patients with hematologic malignancies,”
said Michael Giordano, senior vice president, Head of Development,
Oncology, Bristol-Myers Squibb. “Furthermore, we are committed to
evaluating a broad range of rational combinations that have the
potential to change long-term expectations for patients living with
hematologic malignancies.”
The full set of data to be presented by Bristol-Myers Squibb
includes:
Title
Date/Time
Multiple Myeloma
ELOQUENT-2 update: A phase 3,
randomized,
open-label study of elotuzumab in
combination
with lenalidomide/ dexamethasone in
patients with
R/R MM: 3-year follow-up
Abstract #28
Oral Presentation
Saturday, December 5
8:15-8:30 a.m. EST
Elotuzumab plus bortezomib and
dexamethasone
versus bortezomib and examethasone in
patients
with R/R MM: 2-year follow-up
Abstract #510
Oral Presentation
Monday, December 7
8:15-8:30 a.m.
Effects of elotuzumab on soluble SLAMF7
levels
in multiple myeloma
Abstract #2964
Poster presentation
Sunday, December 6
6:00-8:00 p.m. EST
An ongoing multinational observational
study in
multiple myeloma (PREAMBLE):
Preliminary
report on patient survival
Abstract #2093
Poster presentation
Saturday, December 5
5:30-7:30 p.m. EST
Economic impact of disease progression
(DP) in
Medicare patients with multiple myeloma
(MM)
Abstract #2116
Assessing the economic burden in
Medicare
patients with multiple myeloma
Abstract #2100
Lymphoma
Clinical Outcomes in patients with
Hodgkin
lymphoma responsive to nivolumab in a
phase 1
study (CA209-039): Results of extended
follow-up
Abstract #583
Oral Presentation
Monday, December 7
10:30-10:45 a.m. EST
Chronic Myeloid Leukemia
Economic burden of adverse events in
patients
with chronic myelogenous leukemia
(CML)
treated with BCR-ABL tyrosine kinase
inhibitors
(TKI)
Abstract #876
Oral Presentation
Monday, December 7
5:45–6:00 p.m. EST
Dasatinib in patients with chronic phase
chronic
myeloid leukemia (CML-CP) with persistent,
low-
grade nonhematologic toxicity to imatinib:
Results
from DASPERSE (CA180-400)
Abstract #1575
Poster Presentation
Saturday, December 5
5:30-7:30 p.m. EST
Evaluation of cardiovascular disease risk
in
chronic myelogenous leukemia patients
using
electronic medical records from
community-based
oncology practices
Abstract #4478
Poster Presentation
Monday, December 7
6:00-8:00 p.m. EST
About Elotuzumab
Elotuzumab 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 is
also expressed on Natural Killer cells, plasma cells, and at lower
levels on specific immune cell subsets of differentiated cells
within the hematopoietic lineage.
Elotuzumab has a dual mechanism-of-action. It directly activates
the immune system through Natural Killer cells via the SLAMF7
pathway. Elotuzumab 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 elotuzumab,
with Bristol-Myers Squibb solely responsible for commercial
activities. Elotuzumab was granted Breakthrough Therapy Designation
by the U.S. Food and Drug Administration (FDA) for use in
combination with lenalidomide and dexamethasone for the treatment
of multiple myeloma in patients who have received one to three
prior therapies. According to the FDA, Breakthrough Therapy
Designation is intended to expedite the development and review of
drugs for serious or life-threatening conditions. The criteria for
Breakthrough Therapy Designation requires preliminary clinical
evidence that demonstrates the drug may have substantial
improvement on at least one clinically significant endpoint over
available therapy.
About Opdivo
Bristol-Myers Squibb has a broad, global development program to
study Opdivo in multiple tumor types consisting of more than 50
trials – as monotherapy or in combination with other therapies – in
which more than 8,000 patients have been enrolled worldwide. Opdivo
is the first PD-1 immune checkpoint inhibitor to receive regulatory
approval anywhere in the world in July 2014, and currently has
regulatory approval in 40 countries including the United States,
Japan, and in the European Union.
INDICATIONS and IMPORTANT SAFETY INFORMATION for OPDIVO
(nivolumab)
INDICATIONS
OPDIVO® (nivolumab) as a single agent is indicated for the
treatment of patients with BRAF V600 wild-type unresectable or
metastatic melanoma.
OPDIVO® (nivolumab) as a single agent is indicated for the
treatment of patients with unresectable or metastatic, BRAF V600
mutation-positive melanoma and disease progression following
ipilimumab and a BRAF inhibitor. This indication is approved under
accelerated approval based on tumor response rate and durability of
response. Continued approval for this indication may be contingent
upon verification and description of clinical benefit in the
confirmatory trials.
OPDIVO® (nivolumab), in combination with (ipilimumab), is
indicated for the treatment of patients with BRAF V600 wild-type,
unresectable or metastatic melanoma. This indication is approved
under accelerated approval based on tumor response rate and
durability of response. Continued approval for this indication may
be contingent upon verification and description of clinical benefit
in the confirmatory trials.
OPDIVO® (nivolumab) is indicated for the treatment of
patients with metastatic non-small cell lung cancer (NSCLC) with
progression on or after platinum-based chemotherapy. Patients with
EGFR or ALK genomic tumor aberrations should have disease
progression on FDA-approved therapy for these aberrations prior to
receiving OPDIVO.
OPDIVO® (nivolumab) is indicated for the treatment of
patients with advanced renal cell carcinoma (RCC) who have received
prior anti-angiogenic therapy.
IMPORTANT SAFETY INFORMATION
WARNING: IMMUNE-MEDIATED ADVERSE REACTIONS
YERVOY can result in severe and fatal immune-mediated adverse
reactions. These immune-mediated reactions may involve any organ
system; however, the most common severe immune-mediated adverse
reactions are enterocolitis, hepatitis, dermatitis (including toxic
epidermal necrolysis), neuropathy, and endocrinopathy. The majority
of these immune-mediated reactions initially manifested during
treatment; however, a minority occurred weeks to months after
discontinuation of YERVOY.
Assess patients for signs and symptoms of enterocolitis,
dermatitis, neuropathy, and endocrinopathy and evaluate clinical
chemistries including liver function tests (LFTs),
adrenocorticotropic hormone (ACTH) level, and thyroid function
tests at baseline and before each dose.
Permanently discontinue YERVOY and initiate systemic
high-dose corticosteroid therapy for severe immune-mediated
reactions.
Immune-Mediated Pneumonitis
Immune-mediated pneumonitis or interstitial lung disease,
including fatal cases, occurred with OPDIVO treatment. Across the
clinical trial experience with solid tumors, fatal immune-mediated
pneumonitis occurred with OPDIVO. In addition, in Checkmate 069,
there were six patients who died without resolution of abnormal
respiratory findings. Monitor patients for signs with radiographic
imaging and symptoms of pneumonitis. Administer corticosteroids for
Grade 2 or greater pneumonitis. Permanently discontinue for Grade 3
or 4 and withhold until resolution for Grade 2. In Checkmate 037,
pneumonitis, including interstitial lung disease, occurred in 3.4%
(9/268) of patients receiving OPDIVO and none of the 102 patients
receiving chemotherapy. Immune-mediated pneumonitis occurred in
2.2% (6/268) of patients receiving OPDIVO: Grade 3 (n=1) and Grade
2 (n=5). In Checkmate 066, immune-mediated pneumonitis occurred in
1.4% (3/206) of patients receiving OPDIVO and in none of the 205
patients receiving dacarbazine: Grade 2 (n=3). In Checkmate 057,
immune-mediated pneumonitis, including interstitial lung disease,
occurred in 3.4% (10/287) of patients: Grade 3 (n=5), Grade 2
(n=2), and Grade 1 (n=3). In Checkmate 025, pneumonitis, including
interstitial lung disease, occurred in 5% (21/406) of patients
receiving OPDIVO and 18% (73/397) of patients receiving everolimus.
Immune-mediated pneumonitis occurred in 4.4% (18/406) of patients
receiving OPDIVO: Grade 4 (n=1), Grade 3 (n=4), Grade 2 (n=12), and
Grade 1 (n=1). In Checkmate 069, pneumonitis, including
interstitial lung disease, occurred in 10% (9/94) of patients
receiving OPDIVO in combination with YERVOY and 2.2% (1/46) of
patients receiving YERVOY. Immune-mediated pneumonitis occurred in
6% (6/94) of patients receiving OPDIVO in combination with YERVOY:
Grade 5 (n=1), Grade 3 (n=2) and Grade 2 (n=3).
Immune-Mediated Colitis
Immune-mediated colitis can occur with OPDIVO treatment. Monitor
patients for signs and symptoms of colitis. Administer
corticosteroids for Grade 2 (of more than 5 days duration), 3, or 4
colitis. As a single agent, withhold OPDIVO for Grade 2 or 3 and
permanently discontinue for Grade 4 or recurrent colitis upon
restarting OPDIVO. In combination with YERVOY, withhold OPDIVO for
Grade 2 and permanently discontinue for Grade 3 or 4 or recurrent
colitis upon restarting OPDIVO. In Checkmate 037, diarrhea or
colitis occurred in 21% (57/268) of patients receiving OPDIVO and
18% (18/102) of patients receiving chemotherapy. Immune-mediated
colitis occurred in 2.2% (6/268) of patients receiving OPDIVO;
Grade 3 (n=5) and Grade 2 (n=1). In Checkmate 066, diarrhea or
colitis occurred in 28% (58/206) of patients receiving OPDIVO and
25% (52/205) of patients receiving dacarbazine. Immune-mediated
colitis occurred in 4.9% (10/206) of patients receiving OPDIVO:
Grade 3 (n=5) and Grade 2 (n=5). In Checkmate 057, diarrhea or
colitis occurred in 17% (50/287) of patients receiving OPDIVO.
Immune-mediated colitis occurred in 2.4% (7/287) of patients: Grade
3 (n=3), Grade 2 (n=2), and Grade 1 (n=2). In Checkmate 025,
diarrhea or colitis occurred in 25% (100/406) of patients receiving
OPDIVO and 32% (126/397) of patients receiving everolimus.
Immune-mediated diarrhea or colitis occurred in 3.2% (13/406) of
patients receiving OPDIVO: Grade 3 (n=5), Grade 2 (n=7), and Grade
1 (n=1). In Checkmate 069, diarrhea or colitis occurred in 57%
(54/94) of patients receiving OPDIVO in combination with YERVOY and
46% (21/46) of patients receiving YERVOY. Immune-mediated colitis
occurred in 33% (31/94) of patients receiving OPDIVO in combination
with YERVOY: Grade 4 (n=1), Grade 3 (n=16), Grade 2 (n=9), and
Grade 1 (n=5).
In a separate Phase 3 study of YERVOY 3 mg/kg, severe,
life-threatening, or fatal (diarrhea of ≥7 stools above baseline,
fever, ileus, peritoneal signs; Grade 3-5) immune-mediated
enterocolitis occurred in 34 (7%) patients. Across all
YERVOY-treated patients in that study (n=511), 5 (1%) developed
intestinal perforation, 4 (0.8%) died as a result of complications,
and 26 (5%) were hospitalized for severe enterocolitis.
Immune-Mediated Hepatitis
Immune-mediated hepatitis can occur with OPDIVO treatment.
Monitor patients for abnormal liver tests prior to and periodically
during treatment. Administer corticosteroids for Grade 2 or greater
transaminase elevations. Withhold for Grade 2 and permanently
discontinue for Grade 3 or 4 immune-mediated hepatitis. In
Checkmate 037, there was an increased incidence of liver test
abnormalities in the OPDIVO-treated group as compared to the
chemotherapy-treated group, with increases in AST (28% vs 12%),
alkaline phosphatase (22% vs 13%), ALT (16% vs 5%), and total
bilirubin (9% vs 0). Immune-mediated hepatitis occurred in 1.1%
(3/268) of patients receiving OPDIVO; Grade 3 (n=2) and Grade 2
(n=1). In Checkmate 066, there was an increased incidence of liver
test abnormalities in the OPDIVO-treated group as compared to the
dacarbazine-treated group, with increases in ALT (25% vs. 19%), AST
(24% vs. 19%), alkaline phosphatase (21% vs. 14%), and total
bilirubin (13% vs. 6%). Immune-mediated hepatitis occurred in 0.9%
(2/206) of patients receiving OPDIVO: Grade 3 (n=1) and Grade 2
(n=1). In Checkmate 057, one patient (0.3%) developed
immune-mediated hepatitis. In Checkmate 025, there was an increased
incidence of liver test abnormalities compared to baseline in AST
(33% vs 39%), alkaline phosphatase (32% vs 32%), ALT (22% vs 31%),
and total bilirubin (9% vs 3.5%) in the OPDIVO-treated and
everolimus-treated groups, respectively. Immune-mediated hepatitis
requiring systemic immunosuppression occurred in 1.5% (6/406) of
patients receiving OPDIVO: Grade 3 (n=5) and Grade 2 (n=1). In
Checkmate 069, immune-mediated hepatitis occurred in 15% (14/94) of
patients receiving OPDIVO in combination with YERVOY: Grade 4
(n=3), Grade 3 (n=9), and Grade 2 (n=2).
In a separate Phase 3 study of YERVOY 3 mg/kg, severe,
life-threatening, or fatal hepatotoxicity (AST or ALT elevations
>5x the ULN or total bilirubin elevations >3x the ULN; Grade
3-5) occurred in 8 (2%) patients, with fatal hepatic failure in
0.2% and hospitalization in 0.4%.
Immune-Mediated Dermatitis
In a separate Phase 3 study of YERVOY 3 mg/kg, severe,
life-threatening, or fatal immune-mediated dermatitis (eg,
Stevens-Johnson syndrome, toxic epidermal necrolysis, or rash
complicated by full thickness dermal ulceration, or necrotic,
bullous, or hemorrhagic manifestations; Grade 3-5) occurred in 13
(2.5%) patients. 1 (0.2%) patient died as a result of toxic
epidermal necrolysis. 1 additional patient required hospitalization
for severe dermatitis.
Immune-Mediated Neuropathies
In a separate Phase 3 study of YERVOY 3 mg/kg, 1 case of fatal
Guillain-Barré syndrome and 1 case of severe (Grade 3) peripheral
motor neuropathy were reported.
Immune-Mediated Endocrinopathies
Hypophysitis, adrenal insufficiency, thyroid disorders, and type
1 diabetes mellitus can occur with OPDIVO treatment. Monitor
patients for signs and symptoms of hypophysitis, signs and symptoms
of adrenal insufficiency during and after treatment, thyroid
function prior to and periodically during treatment, and
hyperglycemia. Administer corticosteroids for Grade 2 or greater
hypophysitis. Withhold for Grade 2 or 3 and permanently discontinue
for Grade 4 hypophysitis. Administer corticosteroids for Grade 3 or
4 adrenal insufficiency. Withhold for Grade 2 and permanently
discontinue for Grade 3 or 4 adrenal insufficiency. Administer
hormone-replacement therapy for hypothyroidism. Initiate medical
management for control of hyperthyroidism. Administer insulin for
type 1 diabetes. Withhold OPDIVO for Grade 3 and permanently
discontinue for Grade 4 hyperglycemia.
In Checkmate 025, hypophysitis occurred in 0.5% (2/406) of
patients receiving OPDIVO: Grade 3 (n=1) and Grade 1 (n=1). In
Checkmate 069, hypophysitis occurred in 13% (12/94) of patients
receiving OPDIVO in combination with YERVOY: Grade 3 (n=2) and
Grade 2 (n=10). In Checkmate 037, 066, 057, <1.0% of
OPDIVO-treated patients developed adrenal insufficiency. In
Checkmate 025, adrenal insufficiency occurred in 2.0% (8/406) of
patients receiving OPDIVO: Grade 3 (n=3), Grade 2 (n=4), and Grade
1 (n=1). In Checkmate 069, adrenal insufficiency occurred in 9%
(8/94) of patients receiving OPDIVO in combination with YERVOY:
Grade 3 (n=3), Grade 2 (n=4), and Grade 1 (n=1). In Checkmate 037,
Grade 1 or 2 hypothyroidism occurred in 8% (21/268) of patients
receiving OPDIVO and none of the 102 patients receiving
chemotherapy. Grade 1 or 2 hyperthyroidism occurred in 3.0% (8/268)
of patients receiving OPDIVO and 1.0% (1/102) of patients receiving
chemotherapy. In Checkmate 066, hypothyroidism occurred in 7%
(14/206) of patients receiving OPDIVO (Grade 3 (n=1)) and 0.9%
(2/205) of patients receiving dacarbazine. Hyperthyroidism occurred
in 4.4% (9/206) of patients receiving OPDIVO (Grade 3 (n=1)) and
0.9% (2/205) of patients receiving dacarbazine. In Checkmate 057,
Grade 1 or 2 hypothyroidism, including thyroiditis, occurred in 7%
(20/287) and elevated TSH occurred in 17% of patients receiving
OPDIVO. Grade 1 or 2 hyperthyroidism occurred in 1.4% (4/287) of
patients. In Checkmate 025, thyroid disease occurred in 11%
(43/406) of patients receiving OPDIVO, including one Grade 3 event,
and in 3.0% (12/397) of patients receiving everolimus.
Hypothyroidism/thyroiditis occurred in 8% (33/406) of patients
receiving OPDIVO: Grade 3 (n=2), Grade 2 (n=17), and Grade 1
(n=14). Hyperthyroidism occurred in 2.5% (10/406) of patients
receiving OPDIVO: Grade 2 (n=5) and Grade 1 (n=5). In Checkmate
069, hypothyroidism occurred in 19% (18/94) of patients receiving
OPDIVO in combination with YERVOY. All were Grade 1 or 2 in
severity except for one patient who experienced Grade 3 autoimmune
thyroiditis. Grade 1 hyperthyroidism occurred in 2.1% (2/94) of
patients receiving OPDIVO in combination with YERVOY. In Checkmate
066, diabetes mellitus or diabetic ketoacidosis occurred in 1.0%
(2/206) of patients receiving OPDIVO and none of the 205 receiving
dacarbazine; Grade 3 diabetic ketoacidosis (n=1) and Grade 2
diabetes mellitus (n=1). In Checkmate 025, hyperglycemic adverse
events occurred in 9% (37/406) patients. Diabetes mellitus or
diabetic ketoacidosis occurred in 1.5% (6/406) of patients
receiving OPDIVO: Grade 3 (n=3), Grade 2 (n=2), and Grade 1
(n=1).
In a separate Phase 3 study of YERVOY 3 mg/kg, severe to
life-threatening immune-mediated endocrinopathies (requiring
hospitalization, urgent medical intervention, or interfering with
activities of daily living; Grade 3-4) occurred in 9 (1.8%)
patients. All 9 patients had hypopituitarism, and some had
additional concomitant endocrinopathies such as adrenal
insufficiency, hypogonadism, and hypothyroidism. 6 of the 9
patients were hospitalized for severe endocrinopathies.
Immune-Mediated Nephritis and Renal Dysfunction
Immune-mediated nephritis can occur with OPDIVO treatment.
Monitor patients for elevated serum creatinine prior to and
periodically during treatment. For Grade 2 or 3 increased serum
creatinine, withhold and administer corticosteroids; if worsening
or no improvement occurs, permanently discontinue. Administer
corticosteroids for Grade 4 serum creatinine elevation and
permanently discontinue. In Checkmate 037, there was an increased
incidence of elevated creatinine in the OPDIVO-treated group as
compared to the chemotherapy-treated group (13% vs 9%). Grade 2 or
3 immune-mediated nephritis or renal dysfunction occurred in 0.7%
(2/268) of patients. In Checkmate 066, there was an increased
incidence of elevated creatinine in the OPDIVO-treated group as
compared to the dacarbazine-treated group (11% vs. 10%). Grade 3
immune-mediated renal dysfunction occurred in 0.5% (1/206) of
patients. In Checkmate 057, Grade 2 immune-mediated renal
dysfunction occurred in 0.3% (1/287) of patients receiving OPDIVO.
In Checkmate 025, renal injury occurred in 7% (27/406) of patients
receiving OPDIVO and 3.0% (12/397) of patients receiving
everolimus. Immune-mediated nephritis and renal dysfunction
occurred in 3.2% (13/406) of patients receiving OPDIVO: Grade 5
(n=1), Grade 4 (n=1), Grade 3 (n=5), and Grade 2 (n=6). In
Checkmate 069, Grade 2 or higher immune-mediated nephritis or renal
dysfunction occurred in 2.1% (2/94) of patients. One patient died
without resolution of renal dysfunction.
Immune-Mediated Rash
Immune-mediated rash can occur with OPDIVO treatment. Severe
rash (including rare cases of fatal toxic epidermal necrolysis)
occurred in the clinical program of OPDIVO. Monitor patients for
rash. Administer corticosteroids for Grade 3 or 4 rash. Withhold
for Grade 3 and permanently discontinue for Grade 4. In Checkmate
057, immune-mediated rash occurred in 6% (17/287) of patients
receiving OPDIVO including four Grade 3 cases. In Checkmate 025,
rash occurred in 28% (112/406) of patients receiving OPDIVO and 36%
(143/397) of patients receiving everolimus. Immune-mediated rash,
defined as a rash treated with systemic or topical corticosteroids,
occurred in 7% (30/406) of patients receiving OPDIVO: Grade 3
(n=4), Grade 2 (n=7), and Grade 1 (n=19). In Checkmate 069,
immune-mediated rash occurred in 37% (35/94) of patients receiving
OPDIVO in combination with YERVOY: Grade 3 (n=6), Grade 2 (n=10),
and Grade 1 (n=19).
Immune-Mediated Encephalitis
Immune-mediated encephalitis can occur with OPDIVO treatment.
Withhold OPDIVO in patients with new-onset moderate to severe
neurologic signs or symptoms and evaluate to rule out other causes.
If other etiologies are ruled out, administer corticosteroids and
permanently discontinue OPDIVO for immune-mediated encephalitis.
Across clinical trials of 8490 patients receiving OPDIVO as a
single agent or in combination with YERVOY, <1.0% of patients
were identified as having encephalitis. In Checkmate 057, fatal
limbic encephalitis occurred in one patient (0.3%) receiving
OPDIVO.
Other Immune-Mediated Adverse Reactions
Based on the severity of adverse reaction, permanently
discontinue or withhold treatment, administer high-dose
corticosteroids, and, if appropriate, initiate hormone-replacement
therapy. The following clinically significant immune-mediated
adverse reactions occurred in <1.0% of OPDIVO-treated patients:
uveitis, pancreatitis, facial and abducens nerve paresis,
demyelination, polymyalgia rheumatica, autoimmune neuropathy,
Guillain-Barre syndrome, hypopituitarism and systemic inflammatory
response syndrome. Across clinical trials of OPDIVO administered as
a single agent at doses 3 mg/kg and 10 mg/kg, additional clinically
significant, immune-mediated adverse reactions were identified:
motor dysfunction, vasculitis, and myasthenic syndrome. Across
clinical trials of OPDIVO in combination with YERVOY, the following
additional clinically significant, immune-mediated adverse
reactions were identified: sarcoidosis, duodenitis, and
gastritis.
Infusion Reactions
Severe infusion reactions have been reported in <1.0% of
patients in clinical trials of OPDIVO as a single agent.
Discontinue OPDIVO in patients with Grade 3 or 4 infusion
reactions. Interrupt or slow the rate of infusion in patients with
Grade 1 or 2. In Checkmate 057 and 066, Grade 2 infusion reactions
occurred in 1.0% (5/493) of patients receiving OPDIVO. In Checkmate
025, hypersensitivity/infusion-related reactions occurred in 6%
(25/406) of patients receiving OPDIVO and 1.0% (4/397) of patients
receiving everolimus. In Checkmate 069, Grade 2 infusion reactions
occurred in 3.2% (3/94) of patients receiving OPDIVO in combination
with YERVOY.
Embryofetal Toxicity
Based on their mechanisms of action, OPDIVO and YERVOY can cause
fetal harm when administered to a pregnant woman. Advise pregnant
women of the potential risk to a fetus. Advise females of
reproductive potential to use effective contraception during
treatment with an OPDIVO- or YERVOY- containing regimen and for at
least 5 months after the last dose of OPDIVO.
Lactation
It is not known whether OPDIVO or YERVOY is present in human
milk. Because many drugs, including antibodies, are excreted in
human milk and because of the potential for serious adverse
reactions in nursing infants from OPDIVO-containing regimen, advise
women to discontinue breastfeeding during treatment. Advise women
to discontinue nursing during treatment with YERVOY and for 3
months following the final dose.
Serious Adverse Reactions
In Checkmate 037, serious adverse reactions occurred in 41% of
patients receiving OPDIVO. Grade 3 and 4 adverse reactions occurred
in 42% of patients receiving OPDIVO. The most frequent Grade 3 and
4 adverse drug reactions reported in 2% to <5% of patients
receiving OPDIVO were abdominal pain, hyponatremia, increased
aspartate aminotransferase, and increased lipase. In Checkmate 066,
serious adverse reactions occurred in 36% of patients receiving
OPDIVO. Grade 3 and 4 adverse reactions occurred in 41% of patients
receiving OPDIVO. The most frequent Grade 3 and 4 adverse reactions
reported in ≥2% of patients receiving OPDIVO were
gamma-glutamyltransferase increase (3.9%) and diarrhea (3.4%). In
Checkmate 057, serious adverse reactions occurred in 47% of
patients receiving OPDIVO. The most frequent serious adverse
reactions reported in ≥2% of patients were pneumonia, pulmonary
embolism, dyspnea, pleural effusion, and respiratory failure. In
Checkmate 025, serious adverse reactions occurred in 47% of
patients receiving OPDIVO. The most frequent serious adverse
reactions reported in ≥2% of patients were acute kidney injury,
pleural effusion, pneumonia, diarrhea, and hypercalcemia. In
Checkmate 069, serious adverse reactions occurred in 62% of
patients receiving OPDIVO; the most frequent serious adverse events
with OPDIVO in combination with YERVOY, as compared to YERVOY
alone, were colitis (17% vs 9%), diarrhea (9% vs 7%), pyrexia (6%
vs 7%), and pneumonitis (5% vs 0).
Common Adverse Reactions
In Checkmate 037, the most common adverse reaction (≥20%)
reported with OPDIVO was rash (21%). In Checkmate 066, the most
common adverse reactions (≥20%) reported with OPDIVO vs dacarbazine
were fatigue (49% vs 39%), musculoskeletal pain (32% vs 25%), rash
(28% vs 12%), and pruritus (23% vs 12%). In Checkmate 057, the most
common adverse reactions (≥20%) reported with OPDIVO were fatigue
(49%), musculoskeletal pain (36%), cough (30%), decreased appetite
(29%), and constipation (23%). In Checkmate 025, the most common
adverse reactions (≥20%) reported in patients receiving OPDIVO vs
everolimus were asthenic conditions (56% vs 57%), cough (34% vs
38%), nausea (28% vs 29%), rash (28% vs 36%), dyspnea (27% vs 31%),
diarrhea (25% vs 32%), constipation (23% vs 18%), decreased
appetite (23% vs 30%), back pain (21% vs 16%), and arthralgia (20%
vs 14%). In Checkmate 069, the most common adverse reactions (≥20%)
reported in patients receiving OPDIVO in combination with YERVOY vs
YERVOY alone were rash (67% vs 57%), pruritus (37% vs 26%),
headache (24% vs 20%), vomiting (23% vs 15%), and colitis (22% vs
11%).
In a separate Phase 3 study of YERVOY 3 mg/kg, the most common
adverse reactions (≥5%) in patients who received YERVOY at
3 mg/kg were fatigue (41%), diarrhea (32%), pruritus (31%),
rash (29%), and colitis (8%).
Please see U.S. Full Prescribing Information,
including Boxed WARNING regarding immune-mediated adverse reactions
for YERVOY.
Please see U.S. Full Prescribing Information
for OPDIVO
About Sprycel
Sprycel was first approved by the FDA in 2006 for the treatment
of adults with Philadelphia chromosome–positive (Ph+) chronic
myeloid leukemia (CML) in chronic phase (CP) who are resistant or
intolerant to prior therapy including imatinib. At that time,
Sprycel was also approved for adults with Ph+ acute lymphoblastic
leukemia (ALL) who are resistant or intolerant to prior therapy. It
is the first and only BCR-ABL kinase inhibitor with survival data
in its label for CP Ph+ CML patients who are resistant or
intolerant to Gleevec® (imatinib mesylate). Sprycel is approved and
marketed worldwide for these indications in more than 60
countries.
Sprycel is also an FDA-approved treatment for adults with newly
diagnosed CP Ph+ CML (since October 2010). Sprycel received
accelerated FDA approval for this indication. Additional country
approvals for this indication total more than 50.
SPRYCEL® (dasatinib) INDICATIONS &
IMPORTANT SAFETY INFORMATION
INDICATIONS
SPRYCEL® (dasatinib) is indicated for the treatment of adults
with:
- Newly diagnosed adults with
Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia
(CML) in chronic phase.
- Adults with chronic, accelerated, or
myeloid or lymphoid blast phase Ph+ CML with resistance or
intolerance to prior therapy including imatinib.
- Adults with Philadelphia
chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) with
resistance or intolerance to prior therapy.
IMPORTANT SAFETY INFORMATION
Myelosuppression:
Treatment with SPRYCEL is associated with severe (NCI CTC Grade
3/4) thrombocytopenia, neutropenia, and anemia, which occur earlier
and more frequently in patients with advanced phase CML or Ph+ ALL
than in patients with chronic phase CML.
- In patients with chronic phase CML,
perform complete blood counts (CBCs) every 2 weeks for 12 weeks,
then every 3 months thereafter, or as clinically indicated.
- In patients with advanced phase CML or
Ph+ ALL, perform CBCs weekly for the first 2 months and then
monthly thereafter, or as clinically indicated.
- Myelosuppression is generally
reversible and usually managed by withholding SPRYCEL temporarily
and/or dose reduction.
- In clinical studies, myelosuppression
may have also been managed by discontinuation of study
therapy.
- Hematopoietic growth factor has been
used in patients with resistant myelosuppression.
Bleeding Related Events:
SPRYCEL caused thrombocytopenia in human subjects. In addition,
dasatinib caused platelet dysfunction in vitro. In all CML or Ph+
ALL clinical studies, ≥grade 3 central nervous system (CNS)
hemorrhages, including fatalities, occurred in <1% of patients
receiving SPRYCEL. Grade 3 or greater gastrointestinal hemorrhage,
including fatalities, occurred in 4% of patients and generally
required treatment interruptions and transfusions. Other cases of
≥grade 3 hemorrhage occurred in 2% of patients.
- Most bleeding events in clinical
studies were associated with severe thrombocytopenia.
- Concomitant medications that inhibit
platelet function or anticoagulants may increase the risk of
hemorrhage.
Fluid Retention:
SPRYCEL may cause fluid retention. After 5 years of follow-up in
the randomized newly diagnosed chronic phase CML study (n=258),
grade 3/4 fluid retention was reported in 5% of patients, including
3% of patients with grade 3/4 pleural effusion. In patients with
newly diagnosed or imatinib resistant or intolerant chronic phase
CML, grade 3/4 fluid retention occurred in 6% of patients treated
with SPRYCEL at the recommended dose (n=548). In patients with
advanced phase CML or Ph+ ALL treated with SPRYCEL at the
recommended dose (n=304), grade 3/4 fluid retention was reported in
8% of patients, including grade 3/4 pleural effusion reported in 7%
of patients.
- Patients who develop symptoms of
pleural effusion or other fluid retention, such as new or worsened
dyspnea on exertion or at rest, pleuritic chest pain, or dry cough
should be evaluated promptly with a chest x-ray or additional
diagnostic imaging as appropriate.
- Fluid retention events were typically
managed by supportive care measures that may include diuretics or
short courses of steroids.
- Severe pleural effusion may require
thoracentesis and oxygen therapy.
- Consider dose reduction or treatment
interruption
Cardiovascular Events:
After 5 years of follow-up in the randomized newly diagnosed
chronic phase CML trial (n=258), the following cardiac adverse
events occurred:
- Cardiac ischemic events (3.9% dasatinib
vs 1.6% imatinib), cardiac related fluid retention (8.5% dasatinib
vs 3.9% imatinib), and conduction system abnormalities, most
commonly arrhythmia and palpitations (7.0% dasatinib vs 5.0%
imatinib). Two cases (0.8%) of peripheral arterial occlusive
disease occurred with imatinib and 2 (0.8%) transient ischemic
attacks occurred with dasatinib.
Monitor patients for signs or symptoms consistent with cardiac
dysfunction and treat appropriately.
Pulmonary Arterial Hypertension (PAH):
SPRYCEL may increase the risk of developing PAH, which may occur
any time after initiation, including after more than 1 year of
treatment. Manifestations include dyspnea, fatigue, hypoxia, and
fluid retention. PAH may be reversible on discontinuation of
SPRYCEL.
- Evaluate patients for signs and
symptoms of underlying cardiopulmonary disease prior to initiating
SPRYCEL and during treatment. If PAH is confirmed, SPRYCEL should
be permanently discontinued.
QT Prolongation:
In vitro data suggest that SPRYCEL has the potential to prolong
cardiac ventricular repolarization (QT interval).
- Most bleeding events in clinical
studies were associated with severe thrombocytopenia.
- Concomitant medications that inhibit
platelet function or anticoagulants may increase the risk of
hemorrhage.
Severe Dermatologic Reactions:
Cases of severe mucocutaneous dermatologic reactions, including
Stevens-Johnson syndrome and erythema multiforme, have been
reported in patients treated with SPRYCEL.
- Discontinue permanently in patients who
experience a severe mucocutaneous reaction during treatment if no
other etiology can be identified.
Tumor Lysis Syndrome (TLS):
TLS has been reported in patients with resistance to prior
imatinib therapy, primarily in advanced phase disease.
- Due to potential for TLS, maintain
adequate hydration, correct uric acid levels prior to initiating
therapy with SPRYCEL, and monitor electrolyte levels.
- Patients with advanced stage disease
and/or high tumor burden may be at increased risk and should be
monitored more frequently.
Embryo-Fetal Toxicity:
Based on limited human data, SPRYCEL can cause fetal harm when
administered to a pregnant woman. Hydrops fetalis, fetal leukopenia
and fetal thrombocytopenia have been reported with maternal
exposure to SPRYCEL. Transplacental transfer of dasatinib has been
measured in fetal plasma and amniotic fluid at concentrations
comparable to those in maternal plasma.
- Advise females of reproductive
potential to avoid pregnancy, which may include the use of
effective contraception, during treatment with SPRYCEL and for 30
days after the final dose.
Lactation:
No data are available regarding the presence of dasatinib in
human milk, the effects of the drug on the breastfed infant or the
effects of the drug on milk production. However, dasatinib is
present in the milk of lactating rats.
- Because of the potential for serious
adverse reactions in nursing infants from SPRYCEL, breastfeeding is
not recommended during treatment with SPRYCEL and for 2 weeks after
the final dose.
Drug Interactions:
SPRYCEL is a CYP3A4 substrate and a weak time-dependent
inhibitor of CYP3A4.
- Drugs that may increase SPRYCEL plasma
concentrations are:
- CYP3A4 inhibitors: Concomitant
use of SPRYCEL and drugs that inhibit CYP3A4 should be avoided. If
administration of a potent CYP3A4 inhibitor cannot be avoided,
close monitoring for toxicity and a SPRYCEL dose reduction should
be considered
- Strong CYP3A4 inhibitors (eg,
ketoconazole, itraconazole, clarithromycin, atazanavir, indinavir,
nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin,
voriconazole). If SPRYCEL must be administered with a strong CYP3A4
inhibitor, a dose decrease or temporary discontinuation should be
considered
- Grapefruit juice may also
increase plasma concentrations of SPRYCEL and should be
avoided
- Drugs that may decrease SPRYCEL plasma
concentrations are:
- CYP3A4 inducers: If SPRYCEL must
be administered with a CYP3A4 inducer, a dose increase in SPRYCEL
should be considered
- Strong CYP3A4 inducers (eg,
dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin,
phenobarbital) should be avoided. Alternative agents with less
enzyme induction potential should be considered. If the dose of
SPRYCEL is increased, the patient should be monitored carefully for
toxicity
- St John’s Wort may decrease
SPRYCEL plasma concentrations unpredictably and should be
avoided
- Antacids may decrease SPRYCEL
drug levels. Simultaneous administration of SPRYCEL and antacids
should be avoided. If antacid therapy is needed, the antacid dose
should be administered at least 2 hours prior to or 2 hours after
the dose of SPRYCEL
- H2 antagonists/proton
pump inhibitors (eg, famotidine and omeprazole): Long-term
suppression of gastric acid secretion by use of H2 antagonists or
proton pump inhibitors is likely to reduce SPRYCEL exposure.
Therefore, concomitant use of H2 antagonists or proton pump
inhibitors with SPRYCEL is not recommended
- Drugs that may have their plasma
concentration altered by SPRYCEL are:
- CYP3A4 substrates (eg,
simvastatin) with a narrow therapeutic index should be administered
with caution in patients receiving SPRYCEL
Adverse Reactions:
- In newly diagnosed chronic phase CML
patients:
- Drug-related serious adverse events
(SAEs) were reported for 16.7% of SPRYCEL-treated patients. Serious
adverse reactions reported in ≥5% of patients included pleural
effusion (5%).
- Most common adverse reactions (≥15%)
included myelosuppression, fluid retention, and diarrhea.
- In patients resistant or intolerant to
prior imatinib therapy:
- Drug-related SAEs were reported for
26.1% of Sprycel-treated patients treated at the recommended dose
of 100 mg once daily in the randomized dose-optimization trial of
patients with chronic phase CML resistant or intolerant to prior
imatinib therapy. Serious adverse reactions reported in ≥5% of
patients included pleural effusion (10%).
- Most common adverse reactions (≥15%)
included myelosuppression, fluid retention events, diarrhea,
headache, fatigue, dyspnea, skin rash, nausea, hemorrhage and
musculoskeletal pain.
Please see the full Prescribing Information
here.
Immuno-Oncology at Bristol-Myers
Squibb
Surgery, radiation, cytotoxic or targeted therapies have
represented the mainstay of cancer treatment over the last several
decades, but long-term survival and a positive quality of life have
remained elusive for many patients with advanced disease.
To address this unmet medical need, Bristol-Myers Squibb is
leading research in an innovative field of cancer research and
treatment known as Immuno-Oncology, which involves agents whose
primary mechanism is to work directly with the body’s immune system
to fight cancer. The company is exploring a variety of compounds
and immunotherapeutic approaches for patients with different types
of cancer, including researching the potential of combining
Immuno-Oncology agents that target different pathways in the
treatment of cancer.
Bristol-Myers Squibb is committed to advancing the science of
Immuno-Oncology, with the goal of changing survival expectations
and the way patients live with cancer.
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 www.bms.com or follow
us on Twitter at http://twitter.com/bmsnews.
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. Among other risks, there can be no guarantee
that elotuzumab will receive regulatory approval or, if approved,
that it will become a commercially successful product or that
Opdivo or Sprycel will receive approval for any additional
indications described herein or, if approved, become commercially
successful in such indications. 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, 2014 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.
Endnotes:
© 2015 Bristol-Myers Squibb Company. All rights reserved.
View source
version on businesswire.com: http://www.businesswire.com/news/home/20151130005235/en/
Bristol-Myers Squibb CompanyMedia:Audrey Abernathy,
609-419-5375 / cell:
919-605-4521audrey.abernathy@bms.comorInvestors:Ranya
Dajani, 609-252-5330, ranya.dajani@bms.comBill Szablewski,
609-252-5894, william.szablewski@bms.com
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