Seven company oral presentations include
first disclosure of data from CheckMate -205, evaluating
Opdivo (nivolumab) as frontline therapy in newly-diagnosed,
untreated patients with advanced-stage classical Hodgkin
lymphoma
Phase 2 data from study CA180-372
evaluating Sprycel (dasatinib) in newly-diagnosed pediatric
acute lymphoblastic leukemia among presentations
Updated safety and efficacy data for
Opdivo in combination with ADCETRIS (brentuximab vedotin) in
relapsed/refractory Hodgkin lymphoma to be presented
Bristol-Myers Squibb Company (NYSE: BMY) announced today 33
presentations from Company-sponsored studies, collaborations and
investigator-sponsored research evaluating Opdivo (nivolumab),
Sprycel (dasatinib) and Empliciti (elotuzumab), will be featured at
the 59th Annual Meeting & Exposition of the American Society of
Hematology (ASH) in Atlanta, Ga. from December 9-12.
Presentations across tumor types, including Hodgkin and
non-Hodgkin lymphomas, leukemia and multiple myeloma, reinforce
Bristol-Myers Squibb’s deep expertise in hematologic cancers and
commitment to advancing science to improve patient outcomes.
Data to be presented by Bristol-Myers Squibb include:
Classical and Non-Hodgkin
Lymphoma
- Results from a phase 1/2 study of
brentuximab vedotin in combination with nivolumab in patients with
relapsed or refractory Hodgkin lymphomaAuthor: A.
HerreraAbstract: #649Oral Session: 624. Hodgkin Lymphoma and T/NK
Cell-Lymphoma-Clinical Studies: Hodgkin Lymphoma Immunotherapy
studies; nodular lymphocyte predominant Hodgkin Lymphoma clinical
studiesMonday, December 11, 10:30 AM EST, Georgia World Congress
Center, Building A, Level 4, Marcus Auditorium
- Nivolumab treatment beyond
investigator-assessed progression: outcomes in patients with
relapsed/refractory classical Hodgkin lymphoma from the phase 2
CheckMate -205 studyAuthor: J. CohenAbstract: #650Oral Session:
624. Hodgkin Lymphoma and T/NK Cell-Lymphoma-Clinical Studies:
Hodgkin Lymphoma Immunotherapy studies; nodular lymphocyte
predominant Hodgkin Lymphoma clinical studiesMonday, December 11,
10:45 AM EST, Georgia World Congress Center, Building A, Level 4,
Marcus Auditorium
- Nivolumab for newly diagnosed
advanced-stage classical Hodgkin lymphoma: results from the phase 2
CheckMate -205 studyAuthor: R. RamchandrenAbstract: #651Oral
Session: 624. Hodgkin Lymphoma and T/NK Cell-Lymphoma-Clinical
Studies: Hodgkin Lymphoma Immunotherapy studies; nodular lymphocyte
predominant Hodgkin Lymphoma clinical studiesMonday, December 11,
11 AM EST, Georgia World Congress Center, Building A, Level 4,
Marcus Auditorium
- Safety and efficacy of the
combination of ibrutinib and nivolumab in patients with relapsed
non-Hodgkin lymphoma or chronic lymphocytic leukemiaAuthor: A.
YounesAbstract: #833Oral Session: 642. CLL: Therapy, excluding
Transplantation: New Agents, Infections and PET/CTMonday, December
11, 5:30 PM EST, Georgia World Congress Center, Building B, Level
5, Murphy BR 3-4
- Expression of major
histocompatibility complex class II, but not MHC class I, predicts
outcome in patients with classical Hodgkin lymphoma treated with
nivolumab (programmed death-1 [PD-1] blockade)Author: M.
RoemerAbstract: #1450Poster Session: 621.
Lymphoma-Genetic/Epigenetic Biology: Poster ISaturday, December 9,
5:30-7:30 PM EST, Georgia World Congress Center, Building A, Level
1, Hall A2
- Cost effectiveness of nivolumab for
the treatment of relapsed/refractory classical Hodgkin lymphoma
after failure of autologous stem cell transplantation and treatment
with brentuximab vedotin treatment in AustraliaAuthor: M.
TanAbstract: #2166Poster Session: 904. Outcomes Research-Malignant
Conditions: Poster ISaturday, December 9, 5:30-7:30 PM EST, Georgia
World Congress Center, Building A, Level 1, Hall A2
- Effect of nivolumab on
patient-reported outcomes in patients with relapsed/refractory
classical Hodgkin lymphoma after autologous transplantation:
results from the multicohort phase 2 CheckMate -205
studyAuthor: A. EngertAbstract: #3441Poster Session: 904.
Outcomes Research-Malignant Conditions: Poster IISunday, December
10, 6-8 PM EST, Georgia World Congress Center, Building A, Level 1,
Hall A2
- Economic burden in U.S. patients
with relapsed or refractory classical Hodgkin lymphoma treated with
brentuximab vedotin or chemotherapy after failure of autologous
hematopoietic cell transplantationAuthor: C. ChenAbstract:
#4705Poster Session: 902. Health Services Research-Malignant
Conditions: Poster IIIMonday, December 11, 6-8 PM EST, Georgia
World Congress Center, Building A, Level 1, Hall A2
Multiple Myeloma
- Elotuzumab plus
lenalidomide/dexamethasone vs Ld in patients with newly diagnosed
multiple myeloma: phase 2, randomized, open-label study in
JapanAuthor: N. TakezakoAbstract: #434Oral Session: 653.
Myeloma: Therapy, excluding Transplantation: Upfront Therapy for
Multiple Myeloma: Induction and MaintenanceSunday, December 10,
12:15 PM EST, Georgia World Congress Center, Building C, Level 1,
Hall C4
- Duration of treatment of multiple
myeloma regimens in patients with relapsed or refractory multiple
myeloma: findings in U.S. clinical practice settingsAuthor: R.
PotluriAbstract: #1844Poster Session: 653. Myeloma: Therapy,
excluding Transplantation: Poster ISaturday, December 9, 5:30-7:30
PM EST, Georgia World Congress Center, Building A, Level 1, Hall
A2
- Treatment sequencing patterns
observed in patients treated initially with
lenalidomide/dexamethasone combination as frontline multiple
myeloma therapyAuthor: C. ChenAbstract: #3127Poster Session:
653. Myeloma: Therapy, excluding Transplantation: Poster IISunday,
December 10, 6-8 PM EST, Georgia World Congress Center, Building A,
Level 1, Hall A2
- Treatment patterns and associated
outcomes in patients with relapsed or refractory multiple myeloma
in the U.S. and non-U.S. countries: findings from
PREAMBLEAuthor: R. VijAbstract: #3123Poster Session: 653.
Myeloma: Therapy, excluding Transplantation: Poster IISunday,
December 10, 6-8 PM EST, Georgia World Congress Center, Building A,
Level 1, Hall A2
- Healthcare resource utilization and
costs associated with different treatment modalities of
relapsed/refractory multiple myeloma patients in the U.S.: findings
from PREAMBLEAuthor: D. KuterAbstract: #3157Poster Session:
653. Myeloma: Therapy, excluding Transplantation: Poster IISunday,
December 10, 6-8 PM EST, Georgia World Congress Center, Building A,
Level 1, Hall A2
Leukemia
- CA180-372: An international
collaborative phase 2 trial of dasatinib and chemotherapy in
pediatric patients with newly diagnosed Philadelphia chromosome
positive acute lymphoblastic leukemiaAuthor: S. HungerAbstract
#98Oral Session: 612. Acute Lymphoblastic Leukemia: Clinical
Studies: Advances in the Treatment of ALLSaturday, December 9, 9:45
AM EST, Georgia World Congress Center, Building C, Level 2, Hall
C211-C213
- Dasatinib discontinuation in
patients with chronic-phase chronic myeloid leukemia and stable
deep molecular responseAuthor: N. ShahAbstract: #314Oral
Session: 632: Chronic Myeloid Leukemia: Therapy: Treatment
Discontinuation, Dose Reduction and Prognostic IndicatorsSunday,
December 10, 7:45 AM EST, Georgia World Congress Center, Building
A, Level 4, Marcus Auditorium
- Impact of earlier vs. later
monitoring on disease progression and economic outcomes among
patients with chronic myeloid leukemia in the real-world
settingAuthor: E. JabbourAbstract: #2175Poster Session: 904.
Outcomes Research—Malignant Conditions: Poster ISaturday, December
9, 5:30-7:30 PM EST, Georgia World Congress Center, Building A,
Level 1, Hall A2
- Cytogenetic and molecular responses
by two years in SIMPLICITY, an observational study of chronic-phase
chronic myeloid leukemia patients in routine clinical
practiceAuthor: J. CortesAbstract: #2894Poster Session: 632.
Chronic Myeloid Leukemia: Therapy: Poster IISunday, December 10,
6-8 PM EST, Georgia World Congress Center, Building A, Level 1,
Hall A2
- Economic modeling of the potential
impact of chronic myeloid leukemia monitoring on healthcare
costsAuthor: E. JabbourAbstract: #3378Poster Session: 902.
Health Services Research—Malignant Conditions: Poster IISunday,
December 10, 6-8 PM EST, Georgia World Congress Center, Building A,
Level 1, Hall A2
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 Opdivo
Opdivo is a programmed death-1 (PD-1) immune checkpoint
inhibitor that is designed to uniquely harness the body’s own
immune system to help restore anti-tumor immune response. By
harnessing the body’s own immune system to fight cancer, Opdivo has
become an important treatment option across multiple cancers.
Opdivo’s leading global development program is based on
Bristol-Myers Squibb’s scientific expertise in the field of
Immuno-Oncology and includes a broad range of clinical trials
across all phases, including Phase 3, in a variety of tumor types.
To date, the Opdivo clinical development program has enrolled more
than 25,000 patients. The Opdivo trials have contributed to gaining
a deeper understanding of the potential role of biomarkers in
patient care, particularly regarding how patients may benefit from
Opdivo across the continuum of PD-L1 expression.
In July 2014, Opdivo was the first PD-1 immune checkpoint
inhibitor to receive regulatory approval anywhere in the world.
Opdivo is currently approved in more than 60 countries, including
the United States, the European Union and Japan. In October 2015,
the company’s Opdivo and Yervoy combination regimen was the first
Immuno-Oncology combination to receive regulatory approval for the
treatment of metastatic melanoma and is currently approved in more
than 50 countries, including the United States and the European
Union.
U.S. FDA-APPROVED INDICATIONS FOR
OPDIVO®
OPDIVO® (nivolumab) as a single agent is indicated for the
treatment of patients with BRAF V600 mutation-positive unresectable
or metastatic melanoma. This indication is approved under
accelerated approval based on progression-free survival. Continued
approval for this indication may be contingent upon verification
and description of clinical benefit in the confirmatory trials.
OPDIVO® (nivolumab) as a single agent is indicated for the
treatment of patients with BRAF V600 wild-type unresectable or
metastatic melanoma.
OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab),
is indicated for the treatment of patients with unresectable or
metastatic melanoma. This indication is approved under accelerated
approval based on progression-free survival. 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.
OPDIVO® (nivolumab) is indicated for the treatment of adult
patients with classical Hodgkin lymphoma (cHL) that has relapsed or
progressed after autologous hematopoietic stem cell transplantation
(HSCT) and brentuximab vedotin or after 3 or more lines of systemic
therapy that includes autologous HSCT. This indication is approved
under accelerated approval based on overall response rate.
Continued approval for this indication may be contingent upon
verification and description of clinical benefit in confirmatory
trials.
OPDIVO® (nivolumab) is indicated for the treatment of patients
with recurrent or metastatic squamous cell carcinoma of the head
and neck (SCCHN) with disease progression on or after
platinum-based therapy.
OPDIVO® (nivolumab) is indicated for the treatment of patients
with locally advanced or metastatic urothelial carcinoma who have
disease progression during or following platinum-containing
chemotherapy or have disease progression within 12 months of
neoadjuvant or adjuvant treatment with platinum-containing
chemotherapy. This indication is approved under accelerated
approval based on tumor response rate and duration of response.
Continued approval for this indication may be contingent upon
verification and description of clinical benefit in confirmatory
trials.
OPDIVO® (nivolumab) is indicated for the treatment of adult and
pediatric (12 years and older) patients with microsatellite
instability high (MSI-H) or mismatch repair deficient (dMMR)
metastatic colorectal cancer (CRC) that has progressed following
treatment with a fluoropyrimidine, oxaliplatin, and irinotecan.
This indication is approved under accelerated approval based on
overall response rate and duration of response. Continued approval
for this indication may be contingent upon verification and
description of clinical benefit in confirmatory trials.
OPDIVO® (nivolumab) is indicated for the treatment of patients
with hepatocellular carcinoma (HCC) who have been previously
treated with sorafenib. 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.
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
OPDIVO can cause immune-mediated pneumonitis. Fatal cases have
been reported. Monitor patients for signs with radiographic imaging
and for symptoms of pneumonitis. Administer corticosteroids for
Grade 2 or more severe pneumonitis. Permanently discontinue for
Grade 3 or 4 and withhold until resolution for Grade 2. In patients
receiving OPDIVO monotherapy, fatal cases of immune-mediated
pneumonitis have occurred. Immune-mediated pneumonitis occurred in
3.1% (61/1994) of patients. In patients receiving OPDIVO with
YERVOY, immune-mediated pneumonitis occurred in 6% (25/407) of
patients.
In Checkmate 205 and 039, pneumonitis, including interstitial
lung disease, occurred in 6.0% (16/266) of patients receiving
OPDIVO. Immune-mediated pneumonitis occurred in 4.9% (13/266) of
patients receiving OPDIVO: Grade 3 (n=1) and Grade 2 (n=12).
Immune-Mediated Colitis
OPDIVO can cause immune-mediated colitis. Monitor patients for
signs and symptoms of colitis. Administer corticosteroids for Grade
2 (of more than 5 days duration), 3, or 4 colitis. Withhold OPDIVO
monotherapy for Grade 2 or 3 and permanently discontinue for Grade
4 or recurrent colitis upon re-initiation of OPDIVO. When
administered with YERVOY, withhold OPDIVO and YERVOY for Grade 2
and permanently discontinue for Grade 3 or 4 or recurrent colitis.
In patients receiving OPDIVO monotherapy, immune-mediated colitis
occurred in 2.9% (58/1994) of patients. In patients receiving
OPDIVO with YERVOY, immune-mediated colitis occurred in 26%
(107/407) of patients including three fatal cases.
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
OPDIVO can cause immune-mediated hepatitis. Monitor patients for
abnormal liver tests prior to and periodically during treatment.
Administer corticosteroids for Grade 2 or greater transaminase
elevations. For patients without HCC, withhold OPDIVO for Grade 2
and permanently discontinue OPDIVO for Grade 3 or 4. For patients
with HCC, withhold OPDIVO and administer corticosteroids if AST/ALT
is within normal limits at baseline and increases to >3 and up
to 5 times the upper limit of normal (ULN), if AST/ALT is >1 and
up to 3 times ULN at baseline and increases to >5 and up to 10
times the ULN, and if AST/ALT is >3 and up to 5 times ULN at
baseline and increases to >8 and up to 10 times the ULN.
Permanently discontinue OPDIVO and administer corticosteroids if
AST or ALT increases to >10 times the ULN or total bilirubin
increases >3 times the ULN. In patients receiving OPDIVO
monotherapy, immune-mediated hepatitis occurred in 1.8% (35/1994)
of patients. In patients receiving OPDIVO with YERVOY,
immune-mediated hepatitis occurred in 13% (51/407) of patients.
In Checkmate 040, immune-mediated hepatitis requiring systemic
corticosteroids occurred in 5% (8/154) of patients receiving
OPDIVO.
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 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
OPDIVO can cause immune-mediated hypophysitis, immune-mediated
adrenal insufficiency, autoimmune thyroid disorders, and Type 1
diabetes mellitus. Monitor patients for signs and symptoms of
hypophysitis, signs and symptoms of adrenal insufficiency, thyroid
function prior to and periodically during treatment, and
hyperglycemia. Administer hormone replacement as clinically
indicated and 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. Withhold OPDIVO for Grade 3 and permanently
discontinue for Grade 4 hyperglycemia.
In patients receiving OPDIVO monotherapy, hypophysitis occurred
in 0.6% (12/1994) of patients. In patients receiving OPDIVO with
YERVOY, hypophysitis occurred in 9% (36/407) of patients. In
patients receiving OPDIVO monotherapy, adrenal insufficiency
occurred in 1% (20/1994) of patients. In patients receiving OPDIVO
with YERVOY, adrenal insufficiency occurred in 5% (21/407) of
patients. In patients receiving OPDIVO monotherapy, hypothyroidism
or thyroiditis resulting in hypothyroidism occurred in 9%
(171/1994) of patients. Hyperthyroidism occurred in 2.7% (54/1994)
of patients receiving OPDIVO monotherapy. In patients receiving
OPDIVO with YERVOY, hypothyroidism or thyroiditis resulting in
hypothyroidism occurred in 22% (89/407) of patients.
Hyperthyroidism occurred in 8% (34/407) of patients receiving
OPDIVO with YERVOY. In patients receiving OPDIVO monotherapy,
diabetes occurred in 0.9% (17/1994) of patients. In patients
receiving OPDIVO with YERVOY, diabetes occurred in 1.5% (6/407) of
patients.
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
OPDIVO can cause immune-mediated nephritis. Monitor patients for
elevated serum creatinine prior to and periodically during
treatment. Administer corticosteroids for Grades 2-4 increased
serum creatinine. Withhold OPDIVO for Grade 2 or 3 and permanently
discontinue for Grade 4 increased serum creatinine. In patients
receiving OPDIVO monotherapy, immune-mediated nephritis and renal
dysfunction occurred in 1.2% (23/1994) of patients. In patients
receiving OPDIVO with YERVOY, immune-mediated nephritis and renal
dysfunction occurred in 2.2% (9/407) of patients.
Immune-Mediated Skin Adverse Reactions and Dermatitis
OPDIVO can cause immune-mediated rash, including Stevens-Johnson
syndrome (SJS) and toxic epidermal necrolysis (TEN), some cases
with fatal outcome. Administer corticosteroids for Grade 3 or 4
rash. Withhold for Grade 3 and permanently discontinue for Grade 4
rash. For symptoms or signs of SJS or TEN, withhold OPDIVO and
refer the patient for specialized care for assessment and
treatment; if confirmed, permanently discontinue. In patients
receiving OPDIVO monotherapy, immune-mediated rash occurred in 9%
(171/1994) of patients. In patients receiving OPDIVO with YERVOY,
immune-mediated rash occurred in 22.6% (92/407) of patients.
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 Encephalitis
OPDIVO can cause immune-mediated encephalitis. Evaluation of
patients with neurologic symptoms may include, but not be limited
to, consultation with a neurologist, brain MRI, and lumbar
puncture. 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. In patients receiving OPDIVO
monotherapy, encephalitis occurred in 0.2% (3/1994) of patients.
Fatal limbic encephalitis occurred in one patient after 7.2 months
of exposure despite discontinuation of OPDIVO and administration of
corticosteroids. Encephalitis occurred in one patient receiving
OPDIVO with YERVOY (0.2%) after 1.7 months of exposure.
Other Immune-Mediated Adverse Reactions
Based on the severity of the adverse reaction, permanently
discontinue or withhold OPDIVO, administer high-dose
corticosteroids, and, if appropriate, initiate hormone-replacement
therapy. Across clinical trials of OPDIVO monotherapy or in
combination with YERVOY, the following clinically significant
immune-mediated adverse reactions, some with fatal outcome,
occurred in <1.0% of patients receiving OPDIVO: myocarditis,
rhabdomyolysis, myositis, uveitis, iritis, pancreatitis, facial and
abducens nerve paresis, demyelination, polymyalgia rheumatica,
autoimmune neuropathy, Guillain-Barré syndrome, hypopituitarism,
systemic inflammatory response syndrome, gastritis, duodenitis,
sarcoidosis, histiocytic necrotizing lymphadenitis (Kikuchi
lymphadenitis), motor dysfunction, vasculitis, and myasthenic
syndrome.
Infusion Reactions
OPDIVO can cause severe infusion reactions, which have been
reported in <1.0% of patients in clinical trials. 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
patients receiving OPDIVO monotherapy, infusion-related reactions
occurred in 6.4% (127/1994) of patients. In patients receiving
OPDIVO with YERVOY, infusion-related reactions occurred in 2.5%
(10/407) of patients.
Complications of Allogeneic HSCT after OPDIVO
Complications, including fatal events, occurred in patients who
received allogeneic HSCT after OPDIVO. Outcomes were evaluated in
17 patients from Checkmate 205 and 039, who underwent allogeneic
HSCT after discontinuing OPDIVO (15 with reduced-intensity
conditioning, 2 with myeloablative conditioning). Thirty-five
percent (6/17) of patients died from complications of allogeneic
HSCT after OPDIVO. Five deaths occurred in the setting of severe or
refractory GVHD. Grade 3 or higher acute GVHD was reported in 29%
(5/17) of patients. Hyperacute GVHD was reported in 20% (n=2) of
patients. A steroid-requiring febrile syndrome, without an
identified infectious cause, was reported in 35% (n=6) of patients.
Two cases of encephalitis were reported: Grade 3 (n=1) lymphocytic
encephalitis without an identified infectious cause, and Grade 3
(n=1) suspected viral encephalitis. Hepatic veno-occlusive disease
(VOD) occurred in one patient, who received reduced-intensity
conditioned allogeneic HSCT and died of GVHD and multi-organ
failure. Other cases of hepatic VOD after reduced-intensity
conditioned allogeneic HSCT have also been reported in patients
with lymphoma who received a PD-1 receptor blocking antibody before
transplantation. Cases of fatal hyperacute GVHD have also been
reported. These complications may occur despite intervening therapy
between PD-1 blockade and allogeneic HSCT.
Follow patients closely for early evidence of transplant-related
complications such as hyperacute GVHD, severe (Grade 3 to 4) acute
GVHD, steroid-requiring febrile syndrome, hepatic VOD, and other
immune-mediated adverse reactions, and intervene promptly.
Embryo-Fetal 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 an 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 (n=268). 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 (n=206). 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 067, serious adverse reactions (73%
and 37%), adverse reactions leading to permanent discontinuation
(43% and 14%) or to dosing delays (55% and 28%), and Grade 3 or 4
adverse reactions (72% and 44%) all occurred more frequently in the
OPDIVO plus YERVOY arm (n=313) relative to the OPDIVO arm (n=313).
The most frequent (≥10%) serious adverse reactions in the OPDIVO
plus YERVOY arm and the OPDIVO arm, respectively, were diarrhea
(13% and 2.6%), colitis (10% and 1.6%), and pyrexia (10% and 0.6%).
In Checkmate 017 and 057, serious adverse reactions occurred in 46%
of patients receiving OPDIVO (n=418). The most frequent serious
adverse reactions reported in at least 2% of patients receiving
OPDIVO were pneumonia, pulmonary embolism, dyspnea, pyrexia,
pleural effusion, pneumonitis, and respiratory failure. In
Checkmate 025, serious adverse reactions occurred in 47% of
patients receiving OPDIVO (n=406). The most frequent serious
adverse reactions reported in ≥2% of patients were acute kidney
injury, pleural effusion, pneumonia, diarrhea, and hypercalcemia.
In Checkmate 205 and 039, adverse reactions leading to
discontinuation occurred in 7% and dose delays due to adverse
reactions occurred in 34% of patients (n=266). Serious adverse
reactions occurred in 26% of patients. The most frequent serious
adverse reactions reported in ≥1% of patients were pneumonia,
infusion-related reaction, pyrexia, colitis or diarrhea, pleural
effusion, pneumonitis, and rash. Eleven patients died from causes
other than disease progression: 3 from adverse reactions within 30
days of the last OPDIVO dose, 2 from infection 8 to 9 months after
completing OPDIVO, and 6 from complications of allogeneic HSCT. In
Checkmate 141, serious adverse reactions occurred in 49% of
patients receiving OPDIVO. The most frequent serious adverse
reactions reported in at least 2% of patients receiving OPDIVO were
pneumonia, dyspnea, respiratory failure, respiratory tract
infection, and sepsis. In Checkmate 275, serious adverse reactions
occurred in 54% of patients receiving OPDIVO (n=270). The most
frequent serious adverse reactions reported in at least 2% of
patients receiving OPDIVO were urinary tract infection, sepsis,
diarrhea, small intestine obstruction, and general physical health
deterioration. In Checkmate 040, serious adverse reactions occurred
in 49% of patients (n=154). The most frequent serious adverse
reactions reported in at least 2% of patients were pyrexia,
ascites, back pain, general physical health deterioration,
abdominal pain, and pneumonia.
Common Adverse Reactions
In Checkmate 037, the most common adverse reaction (≥20%)
reported with OPDIVO (n=268) was rash (21%). In Checkmate 066, the
most common adverse reactions (≥20%) reported with OPDIVO (n=206)
vs dacarbazine (n=205) were fatigue (49% vs 39%), musculoskeletal
pain (32% vs 25%), rash (28% vs 12%), and pruritus (23% vs 12%). In
Checkmate 067, the most common (≥20%) adverse reactions in the
OPDIVO plus YERVOY arm (n=313) were fatigue (59%), rash (53%),
diarrhea (52%), nausea (40%), pyrexia (37%), vomiting (28%), and
dyspnea (20%). The most common (≥20%) adverse reactions in the
OPDIVO (n=313) arm were fatigue (53%), rash (40%), diarrhea (31%),
and nausea (28%). In Checkmate 017 and 057, the most common adverse
reactions (≥20%) in patients receiving OPDIVO (n=418) were fatigue,
musculoskeletal pain, cough, dyspnea, and decreased appetite. In
Checkmate 025, the most common adverse reactions (≥20%) reported in
patients receiving OPDIVO (n=406) vs everolimus (n=397) 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
205 and 039, the most common adverse reactions (≥20%) reported in
patients receiving OPDIVO (n=266) were upper respiratory tract
infection (44%), fatigue (39%), cough (36%), diarrhea (33%),
pyrexia (29%), musculoskeletal pain (26%), rash (24%), nausea (20%)
and pruritus (20%). In Checkmate 141, the most common adverse
reactions (≥10%) in patients receiving OPDIVO were cough and
dyspnea at a higher incidence than investigator’s choice. In
Checkmate 275, the most common adverse reactions (≥ 20%) reported
in patients receiving OPDIVO (n=270) were fatigue (46%),
musculoskeletal pain (30%), nausea (22%), and decreased appetite
(22%). In Checkmate 040, the most common adverse reactions (≥20%)
in patients receiving OPDIVO (n=154) were fatigue (38%),
musculoskeletal pain (36%), abdominal pain (34%), pruritus (27%),
diarrhea (27%), rash (26%), cough (23%), and decreased appetite
(22%). The most common adverse reactions (≥20%) in patients who
received OPDIVO as a single agent were fatigue, rash,
musculoskeletal pain, pruritus, diarrhea, nausea, asthenia, cough,
dyspnea, constipation, decreased appetite, back pain, arthralgia,
upper respiratory tract infection, and pyrexia.
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%).
Checkmate Trials and Patient Populations
Checkmate 067 – advanced melanoma alone or in combination
with YERVOY; Checkmate 037 and 066 – advanced melanoma;
Checkmate 017 – squamous non-small cell lung cancer (NSCLC);
Checkmate 057 – non-squamous NSCLC; Checkmate 025 –
renal cell carcinoma; Checkmate 205/039 – classical Hodgkin
lymphoma; Checkmate 141 – squamous cell carcinoma of the
head and neck; Checkmate 275 – urothelial carcinoma;
Checkmate 040 – hepatocellular carcinoma.
Please see U.S. Full Prescribing Information for OPDIVO and
YERVOY, including Boxed WARNING regarding immune-mediated
adverse reactions for YERVOY.
About Sprycel
Sprycel first received FDA approval 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. 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, and in November 2017, Sprycel received
FDA approval for the expanded indication for treatment in pediatric
patients with CP Ph+ CML. The adult indication is approved in more
than 50 countries.
U.S. FDA-APPROVED INDICATIONS FOR
SPRYCEL ®
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.
- Chronic, accelerated, or myeloid or
lymphoid blast phase Ph+ CML with resistance or intolerance to
prior therapy including imatinib.
- Philadelphia chromosome-positive acute
lymphoblastic leukemia (Ph+ ALL) with resistance or intolerance to
prior therapy.
- Pediatric patients with Philadelphia
chromosome-positive (Ph+) chronic myeloid leukemia (CML) in chronic
phase.
IMPORTANT SAFETY
INFORMATION
Myelosuppression
Treatment with SPRYCEL is associated with severe (NCI CTCAE
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. Myelosuppression
was reported in patients with normal baseline laboratory values as
well as in patients with pre-existing laboratory abnormalities.
- 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 can cause serious and fatal bleeding. In all CML or Ph+
ALL clinical studies, Grade ≥3 central nervous system (CNS)
hemorrhages, including fatalities, occurred in <1% of patients
receiving SPRYCEL. The incidence of Grade 3/4 hemorrhage, occurred
in 5.8% of adult patients and generally required treatment
interruptions and transfusions. The incidence of Grade 5 hemorrhage
occurred in 0.4% of adult patients. The most frequent site of
hemorrhage was gastrointestinal.
- Most bleeding events in clinical
studies were associated with severe thrombocytopenia
- In addition to causing thrombocytopenia
in human subjects, dasatinib caused platelet dysfunction in
vitro
- 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 adult 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 adult
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
adult 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. In pediatric patients with
chronic phase CML cases of Grade 1 or 2 fluid retention were
reported in 10.3% 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
SPRYCEL can cause cardiac dysfunction. After 5 years of
follow-up in the randomized newly diagnosed chronic phase CML trial
in adults (n=258), the following cardiac adverse reactions
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 in adult and
pediatric patients, 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
SPRYCEL may increase the risk of prolongation of QTc in patients
including those with hypokalemia or hypomagnesemia, patients with
congenital long QT syndrome, patients taking antiarrhythmic
medicines or other medicinal products that lead to QT prolongation,
and cumulative high-dose anthracycline therapy
- Correct hypokalemia or hypomagnesemia
prior to and during SPRYCEL administration
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
Effects on Growth and Development in Pediatric Patients
In pediatric trials of SPRYCEL in chronic phase CML after at
least 2 years of treatment, adverse reactions associated with bone
growth and development were reported in 5 (5.2%) patients, one of
which was severe in intensity (Growth Retardation Grade 3). These 5
cases included cases of epiphyses delayed fusion, osteopenia,
growth retardation, and gynecomastia. Of these 5 cases, 1 case of
osteopenia and 1 case of gynecomastia resolved during
treatment.
Lactation
No data are available regarding the presence of dasatinib in
human milk, the effects of the drug on the breastfed child 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 children from SPRYCEL, breastfeeding
is not recommended during treatment with SPRYCEL and for 2 weeks
after the final dose
Drug Interactions
- Strong CYP3A4
inhibitors: The coadministration with strong CYP3A
inhibitors may increase dasatinib concentrations. Increased
dasatinib concentrations may increase the risk of toxicity. Avoid
concomitant use of strong CYP3A4 inhibitors. If concomitant
administration of a strong CYP3A4 inhibitor cannot be avoided,
consider a SPRYCEL dose reduction
- Grapefruit juice may
increase plasma concentrations of SPRYCEL and should be
avoided
- Strong CYP3A4 inducers: The
coadministration of SPRYCEL with strong CYP3A inducers may decrease
dasatinib concentrations. Decreased dasatinib concentrations may
reduce efficacy. Consider alternative drugs with less enzyme
induction potential. If concomitant administration of a strong
CYP3A4 inducer cannot be avoided, consider a SPRYCEL dose increase
- St. John’s wort may
decrease plasma concentrations of SPRYCEL and should be
avoided
- Gastric Acid Reducing
Agents: The coadministration of SPRYCEL with a gastric
acid reducing agent may decrease the concentrations of dasatinib.
Decreased dasatinib concentrations may reduce efficacy.Do not
administer H2 antagonists or proton pump
inhibitors with SPRYCEL. Consider the use of antacids in place of
H2 antagonists or proton pump inhibitors. Administer the
antacid at least 2 hours prior to or 2 hours after the dose of
SPRYCEL. Avoid simultaneous administration of SPRYCEL with
antacids.
Adverse Reactions
The safety data reflects exposure to SPRYCEL at all doses tested
in clinical studies (n=2809) including 324 adult patients with
newly diagnosed chronic phase CML, 2388 adult patients with
imatinib resistant or intolerant chronic or advanced phase CML or
Ph+ ALL, and 97 pediatric patients with chronic phase CML.
The median duration of therapy in a total of 2712
SPRYCEL-treated adult patients was 19.2 months (range 0–93.2
months). Median duration of therapy in:
- 1618 adult patients with chronic phase
CML was 29 months (range 0–92.9 months)
- Median duration for 324 adult patients
in the newly diagnosed chronic phase CML trial was approximately 60
months
- 1094 adult patients with advanced phase
CML or Ph+ ALL was 6.2 months (range 0–93.2 months)
In two non-randomized trials in 97 pediatric patients with
chronic phase CML (51 patients newly diagnosed and 46 patients
resistant or intolerant to previous treatment with imatinib), the
median duration of therapy was 51.1 months (range 1.9 to 99.6
months).
In the newly diagnosed adult chronic phase CML trial, after a
minimum of 60 months of follow-up, the cumulative discontinuation
rate for 258 patients was 39%.
In the overall population of 2712 adult SPRYCEL-treated
patients, 88% of patients experienced adverse reactions at some
time and 19% experienced adverse reactions leading to treatment
discontinuation.
Among the 1618 adult SPRYCEL-treated patients with chronic phase
CML, drug-related adverse reactions leading to discontinuation were
reported in 329 (20.3%) patients.
- In the adult newly diagnosed chronic
phase CML trial, drug was discontinued for adverse reactions in 16%
of SPRYCEL-treated patients with a minimum of 60 months of
follow-up
Among the 1094 SPRYCEL-treated patients with advanced phase CML
or Ph+ ALL, drug-related adverse reactions leading to
discontinuation were reported in 191 (17.5%) patients. Among the 97
pediatric subjects, drug-related adverse reactions leading to
discontinuation were reported in 1 patient (1%).
Patients ≥65 years are more likely to experience the commonly
reported adverse reactions of fatigue, pleural effusion, diarrhea,
dyspnea, cough, lower gastrointestinal hemorrhage, and appetite
disturbance, and more likely to experience the less frequently
reported adverse reactions of abdominal distention, dizziness,
pericardial effusion, congestive heart failure, hypertension,
pulmonary edema and weight decrease, and should be monitored
closely.
- In adult newly diagnosed chronic phase
CML patients:
- Drug-related serious adverse reactions
(SARs) were reported for 16.7% of patients. Serious adverse
reactions reported in ≥5% of patients included pleural effusion
(5%)
- Grade 3/4 laboratory abnormalities
included neutropenia (29%), thrombocytopenia (22%), anemia (13%),
hypophosphatemia (7%), hypocalcemia (4%), elevated bilirubin (1%),
and elevated creatinine (1%)
- In adult patients resistant or
intolerant to prior imatinib therapy:
- Drug-related SARs 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%)
- Grade 3/4 hematologic laboratory
abnormalities in chronic phase CML patients resistant or intolerant
to prior imatinib therapy who received SPRYCEL 100 mg once daily
with a minimum follow up of 60 months included neutropenia (36%),
thrombocytopenia (24%), and anemia (13%). Other grade 3/4
laboratory abnormalities included: hypophosphatemia (10%), and
hypokalemia (2%)
- Among chronic phase CML patients with
resistance or intolerance to prior imatinib therapy, cumulative
grade 3/4 cytopenias were similar at 2 and 5 years including:
neutropenia (36% vs 36%), thrombocytopenia (23% vs 24%), and anemia
(13% vs 13%)
- Grade 3/4 elevations of transaminases
or bilirubin and Grade 3/4 hypocalcemia, hypokalemia, and
hypophosphatemia were reported in patients with all phases of CML
- Elevations in transaminases or
bilirubin were usually managed with dose reduction or
interruption
- Patients developing Grade 3/4
hypocalcemia during the course of SPRYCEL therapy often had
recovery with oral calcium supplementation
- In pediatric subjects with Ph+ CML in
chronic phase
- Drug-related SARs were reported for
14.4% of pediatric patients
- In the pediatric studies, the rates of
laboratory abnormalities were consistent with the known profile for
laboratory parameters in adults
- Most common adverse reactions (≥15%) in
patients included myelosuppression, fluid retention events,
diarrhea, headache, skin rash, hemorrhage, dyspnea, fatigue,
nausea, and musculoskeletal pain
Please see the US full Prescribing
Information here.
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 the Bristol-Myers Squibb and Ono
Pharmaceutical Co., Ltd. Collaboration
In 2011, through a collaboration agreement with Ono
Pharmaceutical Co., Ltd. (Ono), Bristol-Myers Squibb expanded its
territorial rights to develop and commercialize Opdivo globally
except in Japan, South Korea and Taiwan, where Ono had retained all
rights to the compound at the time. On July 23, 2014, Bristol-Myers
Squibb and Ono further expanded the companies’ strategic
collaboration agreement to jointly develop and commercialize
multiple immunotherapies – as single agents and combination
regimens – for patients with cancer in Japan, South Korea and
Taiwan.
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. Among other risks, there can be no guarantee
that Opdivo, Sprycel, Empliciti or any of the compounds mentioned
above will receive regulatory approval in the US for an additional
indication. 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.
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Bristol-Myers Squibb CompanyMedia:Audrey
Abernathy,
919-605-4521audrey.abernathy@bms.comorInvestors:Tim Power,
609-252-7509timothy.power@bms.comorBill Szablewski,
609-252-5894william.szablewski@bms.com
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