New data on Opdivo (nivolumab) plus
Yervoy (ipilimumab) in patients with advanced hepatocellular
carcinoma and in melanoma patients with symptomatic brain
metastases
New long-term survival data and health
outcomes research on Opdivo in combination with Yervoy in
advanced melanoma
Eighteen-month efficacy results for
Empliciti (elotuzumab) plus pomalidomide and low-dose
dexamethasone for relapsed/refractory multiple myeloma
Translational research exploring the use of
novel technologies and artificial intelligence to understand the
association of inflammation gene signatures with tumor immune
cells
Bristol-Myers Squibb Company (NYSE:BMY) today announced the
presentation of data from across the company’s oncology portfolio
at the American Society of Clinical Oncology (ASCO) Annual Meeting
2019 in Chicago, May 31-June 4, and the 24th Annual Congress of the
European Hematology Association (EHA) in Amsterdam, June 13-16.
Data from over 90 Company-sponsored studies, investigator-sponsored
studies and collaborations evaluating oncology compounds and early
translational medicine across 20 types of cancer will be featured
at the two meetings. Presentations will highlight the role of
Immuno-Oncology (I-O) monotherapy and combination approaches in
improving survival and quality of life outcomes, as well as
translational research investigating novel biomarkers and
diagnostics to aid in the selection of tailored treatments for each
patient based on their unique disease biology.
2019 ASCO Annual Meeting - Highlights of Bristol-Myers Squibb
data include:*All times noted are Central Daylight Time
Hepatocellular Carcinoma
- Primary efficacy and safety results
from the Phase 1/2 CheckMate -040 study evaluating the combination
of Opdivo (nivolumab) plus Yervoy (ipilimumab) in patients with
advanced hepatocellular carcinoma, the most common type of liver
cancer, will be presented. These data (Abstract #4012), including
objective response rate and overall survival, will be featured in a
poster display on Monday, June 3 from 8-11 AM CDT, and in a poster
discussion from 3-4:30 PM CDT.
Melanoma
- Safety and efficacy of Opdivo in
combination with Yervoy in patients with symptomatic melanoma brain
metastases (Abstract #9501) will be featured in an oral session on
Tuesday, June 4, from 9:45 AM-12:45 PM CDT.
- New long-term survival data and health
outcomes research evaluating Opdivo in combination with Yervoy in
advanced melanoma—in terms of survival outcomes (CA209-004,
Abstract #9533), quality of life after four years and during the
treatment-free interval following discontinuation of therapy
(CheckMate -067, Abstracts #9551 and #9568), and treatment-free
survival (pooled data from CheckMate -067 and -069, Abstract #
9550) – will be featured in a poster display on Monday, June 3 from
1:15-4:15 PM CDT.
Renal Cell Carcinoma
- Safety and efficacy of Opdivo in
combination with Yervoy in patients with asymptomatic advanced
renal cell carcinoma brain metastases (Abstract #4517) will be
featured in a poster display on Monday, June 3 from 1:15-4:15 PM
CDT, and in a poster discussion from 4:30-6 PM CDT.
Translational Medicine and Tumor
Biology
- Translational data to identify
potentially predictive biomarkers and expand translational research
capabilities will be presented. Through the use of gene expression
profiling (GEP) and machine-learning modeling, a novel,
tumor-associated inflammation gene signature was identified through
correlative, immunohistochemistry assessment of CD8 expression on T
cells. This CD8-derived signature was then used to assess
inflammation of the tumor microenvironment across 12 tumor types
(Abstract #2593). Additionally, using an innovative artificial
intelligence-based approach, combined with T-cell localization gene
signatures by GEP, researchers quantified the abundance of immune
cells and their spatial location within the tumor microenvironment
(Abstract #2594). Both abstracts will be featured in a poster
session on Saturday, June 1 from 8-11 AM CDT.
24th Annual Congress of the EHA - Highlights of
Bristol-Myers Squibb data include:*All times noted are Central
European Standard Time
Multiple Myeloma
- Extended 18-month follow-up data from
the Phase 2 ELOQUENT-3 trial (Abstract #PS1370) evaluating the
addition of Empliciti (elotuzumab) to pomalidomide and low-dose
dexamethasone in relapsed/refractory (R/R) multiple myeloma,
including a descriptive overall survival analysis for the
combination, will be featured in a poster session on Saturday, June
15 from 5:30-7 PM CEST.
Classical Hodgkin and Non-Hodgkin
Lymphoma
- Updated safety and efficacy results in
two patient subgroups from the Phase 2 CheckMate -744 study, the
first risk-stratified, response-adapted study of Opdivo and
ADCETRIS (brentuximab vedotin), followed by ADCETRIS and
bendamustine for suboptimal response, in children, adolescents and
young adults with R/R classical Hodgkin lymphoma (cHL), prior to
autologous stem cell transplantation (Abstract #S822) will be
presented in an oral presentation on Saturday, June 15 from
12:30-12:45 PM CEST.
- Two-year results from cohort D of the
Phase 2 CheckMate -205 study, evaluating Opdivo plus doxorubicin,
vinblastine and dacarbazine in patients with newly diagnosed
advanced-stage cHL (Abstract #S821), will be presented in an oral
presentation on Saturday, June 15 from 12:15-12:30 PM CEST.
- A full analysis of the Phase 1/2
CheckMate -436 study, evaluating Opdivo and ADCETRIS in patients
with R/R primary mediastinal large B-cell lymphoma (Abstract
#S1601), will be presented in an oral presentation on Sunday, June
16 from 9-9:15 AM CEST.
2019 ASCO Annual Meeting - Company-sponsored and
collaborative data include:*All times noted are Central
Daylight Time
Gastrointestinal Malignancies
- Nivolumab (NIVO) + ipilimumab (IPI)
combination therapy in patients (pts) with advanced hepatocellular
carcinoma (aHCC): Results from CheckMate 040 Author:
YauAbstract: #4012Poster Discussion Session: Gastrointestinal
(Noncolorectal) CancerMonday, June 3, Poster Display: 8-11 AM, Hall
ADiscussion: 3-4:30 PM, Arie Crown Theater
- Nivolumab (NIVO) + low-dose
ipilimumab (IPI) as first-line (1L) therapy in microsatellite
instability-high/DNA mismatch repair deficient (MSI-H/dMMR)
metastatic colorectal cancer (mCRC): Clinical update Author:
LenzAbstract: #3521Poster Session: Gastrointestinal (Colorectal)
CancerMonday, June 3, Poster Display: 8-11 AM, Hall A
Melanoma
- Long-term follow-up of CA209-004:
A phase I dose-escalation study of combined nivolumab (NIVO)
and ipilimumab (IPI) in patients with advanced melanoma Author:
AtkinsAbstract: #9533Poster Session: Melanoma/Skin CancersMonday,
June 3, Poster Display: 1:15-4:15 PM, Hall A
- Sensitivity of treatment-free
survival (TFS), a novel outcome, to subgroup analyses of patients
(pts) with advanced melanoma (MEL) treated with immune checkpoint
inhibitors (ICI) Author: MantiaAbstract: #9550Poster Session:
Melanoma/Skin CancersMonday, June 3, Poster Display: 1:15-4:15 PM,
Hall A
- Patient-reported quality of life
(QoL) of advanced melanoma patients in a Phase 3 study of nivolumab
(NIVO) with or without ipilimumab (IPI) versus IPI: CheckMate 067
4-year data Author: SchadendorfAbstract: #9551Poster Session:
Melanoma/Skin CancersMonday, June 3, Poster Display: 1:15-4:15 PM,
Hall A
- Quality of life (QoL) and symptom
burden in patients (pts) with advanced melanoma during the
treatment-free interval (TFI) after discontinuation of nivolumab
(NIVO) or NIVO plus ipilimumab (IPI) Author: TaylorAbstract:
#9568Poster Session: Melanoma/Skin CancersMonday, June 3, Poster
Display: 1:15-4:15 PM, Hall A
- An analysis of nivolumab-mediated
adverse events and association with clinical efficacy in resected
stage III or IV melanoma (CheckMate 238) Author:
MandalaAbstract: #9584Poster Session: Melanoma/Skin CancersMonday,
June 3, Poster Display: 1:15-4:15 PM, Hall A
- Efficacy and safety of the
combination of nivolumab (NIVO) plus ipilimumab (IPI) in patients
with symptomatic melanoma brain metastases (CheckMate 204)
Author: TawbiAbstract: #9501Oral Session: Melanoma/Skin
CancersTuesday, June 4, 9:45 AM-12:45 PM, S406Presentation:
9:57-10:09 AM, S406
Genitourinary Malignancies
- CheckMate 214 post-hoc analyses of
nivolumab plus ipilimumab or sunitinib in IMDC
intermediate/poor-risk patients with previously untreated advanced
renal cell carcinoma with sarcomatoid features Author:
McDermottAbstract: #4513Poster Discussion Session: Genitourinary
(Nonprostate) CancerMonday, June 3, Poster Display: 1:15-4:15 PM,
Hall ADiscussion: 4:30-6 PM, Hall D2
- Safety and efficacy of nivolumab
plus ipilimumab (NIVO+IPI) in patients with advanced renal cell
carcinoma (aRCC) with brain metastases: Interim analysis of
CheckMate 920 Author: EmamekhooAbstract: #4517Poster Discussion
Session: Genitourinary (Nonprostate) CancerMonday, June 3, Poster
Display: 1:15-4:15 PM, Hall ADiscussion: 4:30-6 PM, Hall D2
- Consistent efficacy of nivolumab
plus ipilimumab across number of International Metastatic Database
Consortium (IMDC) risk factors in CheckMate 214 Author:
EscudierAbstract: #4575Poster Session: Genitourinary (Nonprostate)
CancerMonday, June 3, Poster Display: 1:15-4:15 PM, Hall A
- Clinical and economic outcomes
associated with sequential treatment in patients with advanced
renal cell carcinoma (aRCC) Author: ReganAbstract: #4566Poster
Session: Genitourinary (Nonprostate) CancerMonday, June 3, Poster
Display: 1:15-4:15 PM, Hall A
- Nivolumab monotherapy in patients
with advanced platinum-resistant urothelial carcinoma: Efficacy and
safety update from CheckMate 275 Author:
Siefker-RadtkeAbstract: #4524Poster Session: Genitourinary
(Nonprostate) CancerMonday, June 3, Poster Display: 1:15-4:15 PM,
Hall A
- Real-world outcomes with IO
therapies: A prospective observational cohort study in patients
(pts) with advanced melanoma (OPTIMIzE) Author:
KirkwoodAbstract: #e14144Online Only
Translational Medicine and
Biomarkers
- Serum IL-6 and CRP as prognostic
factors in melanoma patients receiving single agent and combination
checkpoint inhibition Author: WeberAbstract: #100Clinical
Science Symposium: Fine-Tuning Checkpoint Inhibition: Biomarkers of
Response and ResistanceSaturday, June 1, Clinical Science
Symposium: 8-9:30 AM, Hall D1Presentation: 8-8:12 AM, Hall D1
- Development of a baseline prognostic
cytokine signature that correlates with nivolumab (NIVO) clearance
(CL): Translational pharmacokinetic/pharmacodynamic (PK/PD)
analysis in patients with renal cell carcinoma (RCC) Author:
WangAbstract: #2544Poster Session: Developmental Immunotherapy and
Tumor ImmunobiologySaturday, June 1, Poster Display: 8-11 AM, Hall
A
- Association of an inflammatory gene
signature with CD8 expression by immunohistochemistry (IHC) in
multiple tumor types Author: SzaboAbstract: #2593Poster
Session: Developmental Immunotherapy and Tumor
ImmunobiologySaturday, June 1, Poster Display: 8-11 AM, Hall A
- CD8+ T cells in tumor parenchyma and
stroma by image analysis (IA) and gene expression profiling (GEP):
Potential biomarkers for immuno-oncology (I-O) therapy Author:
SzaboAbstract: #2594Poster Session: Developmental Immunotherapy and
Tumor ImmunobiologySaturday, June 1, Poster Display: 8-11 AM, Hall
A
- Association of human endogenous
retrovirus (hERV) expression with clinical efficacy of PD-1
blockade in metastatic clear cell renal cell carcinoma (mccRCC)
Author: PignonAbstract: #4568Poster Session: Genitourinary
(Nonprostate) CancerMonday, June 3, Poster Display: 1:15-4:15 PM,
Hall A
New and Early Assets
- Baseline tumor-immune signatures
associated with response to bempegaldesleukin (NKTR-214) and
nivolumab Author: HurwitzAbstract: #2623Poster Session:
Developmental Immunotherapy and Tumor ImmunobiologySaturday, June
1, Poster Display: 8-11 AM, Hall A
- CA224-060: A randomized, open label,
phase II trial of relatlimab (anti-LAG-3) and nivolumab with
chemotherapy versus nivolumab with chemotherapy as first-line
treatment in patients with gastric or gastroesophageal junction
adenocarcinoma Author: FeeneyAbstract: #TPS4143Poster Session:
Gastrointestinal (Noncolorectal) CancerMonday, June 3, Poster
Display: 8-11 AM, Hall A
- CA045-001: A phase III, randomized,
open label study of bempegaldesleukin (NKTR-214) plus nivolumab
(NIVO) versus NIVO monotherapy in patients (pts) with previously
untreated, unresectable or metastatic melanoma (MEL) Author:
KhushalaniAbstract: #TPS9601Poster Session: Melanoma/Skin
CancersMonday, June 3, Poster Display: 1:15-4:15 PM, Hall A
- A phase III randomized open
label study comparing bempegaldesleukin (NKTR-214) plus nivolumab
to sunitinib or cabozantinib (investigator's choice) in patients
with previously untreated advanced renal cell carcinoma Author:
TannirAbstract: #TPS4595Poster Session: Genitourinary (Nonprostate)
CancerMonday, June 3, Poster Display: 1:15-4:15 PM, Hall A
- A phase 3 randomized study of
neoadjuvant chemotherapy (NAC) alone or in combination with
nivolumab (NIVO) ± BMS-986205 in cisplatin-eligible muscle invasive
bladder cancer (MIBC) Author: SonpavdeAbstract: #TPS4587Poster
Session: Genitourinary (Nonprostate) CancerMonday, June 3, Poster
Display: 1:15-4:15 PM, Hall A
Clinical Collaborations
- Preliminary immunogenicity, safety,
and efficacy of JNJ-64041757 (JNJ-757) in non-small cell lung
cancer (NSCLC): Results from two phase 1 studies Author:
BrahmerAbstract: #9093Poster Session: Lung Cancer-Non-Small Cell
MetastaticSunday, June 2, Poster Display: 8-11 AM, Hall A
- An open label, multicenter, phase
I/II study of RP1 as a single agent and in combination with PD1
blockade in patients with solid tumors Author:
MiddletonAbstract: #TPS2671Poster Session: Developmental
Immunotherapy and Tumor ImmunobiologySaturday, June 1, Poster
Display: 8-11 AM, Hall A
- Ph1/2 study of Rova-T in
combination with nivolumab (Nivo) ± ipilimumab (Ipi) for patients
(pts) with 2L+ extensive-stage (ED) SCLC Author:
MalhotraAbstract: #8516Poster Session: Lung Cancer-Non-Small Cell
Local-Regional/Small Cell/Other Thoracic CancersSunday, June 2,
Poster Display: 8-11 AM; Hall ADiscussion: 11:15 AM–12:45 PM,
S406
24th Congress of the EHA - Company-sponsored
and collaborative data include:*All times noted are Central
European Summer Time
Lymphoma
- Nivolumab Plus Doxorubicin,
Vinblastine and Dacarbazine for Newly Diagnosed Advanced-Stage
Classical Hodgkin Lymphoma: 2-Year Extended Follow-Up From Cohort D
of the Phase 2 CheckMate 205 Study Author:
Domingo-DomènechAbstract: #S821Oral Session: Hodgkin lymphoma –
ClinicalSaturday, June 15, 11:30 AM-12:45 PM, Hall 5Presentation:
12:15-12:30 PM, Hall 5
- Nivolumab and Brentuximab
Vedotin-Based, Response-Adapted Treatment in Primary Refractory and
in Pediatric Patients with Relapsed/Refractory Classical Hodgkin
Lymphoma in CheckMate 744 Author: LeBlancAbstract: #S822Oral
Session: Hodgkin lymphoma – ClinicalSaturday, June 15, 11:30
AM-12:45 PM, Hall 5Presentation: 12:30-12:45 PM, Hall 5
- Nivolumab Combined with Brentuximab
Vedotin for Relapsed/Refractory Primary Mediastinal Large B-cell
Lymphoma: Efficacy and Safety Results from the Phase 2 CheckMate
436 Study Author: ZinzaniAbstract: #S1601Oral Session:
Aggressive lymphomas – First line, combination therapy and
real-life dataSunday, June 16, 8-9:15 AM, Hall 5Presentation:
9-9:15 AM, Hall 5
Multiple Myeloma
- Elotuzumab Plus Pomalidomide and
Dexamethasone for Relapsed/Refractory Multiple Myeloma: Efficacy
Results After Additional Follow-Up of the Phase 2, Randomized
ELOQUENT-3 Study Author: DimopoulosAbstract: #PS1370Poster
Session: Myeloma and other monoclonal gammopathies –
ClinicalSaturday, June 15, 5:30-7 PM, Poster Area
- Investigating Mechanisms of
Elotuzumab and Lenalidomide in Multiple Myeloma Author:
RichardsonAbstract: #PF568Poster Session: Myeloma and other
monoclonal gammopathies – Biology & Translational
ResearchFriday, June 14, 5:30-7 PM, Poster Area
- Use of Pomalidomide-Based Regimens
in Relapsed/Refractory Multiple Myeloma in Four European Countries
– Findings From PREAMBLE Author: MoreauAbstract: #PS1405Poster
Session: Myeloma and other monoclonal gammopathies –
ClinicalSaturday, June 15, 5:30-7 PM, Poster Area
Leukemia
- DASCERN 2-Year Extended Follow-Up of
Dasatinib Efficacy and Safety in Patients (Pts) with Chronic
Myeloid Leukemia in Chronic Phase (CML-CP) Who Have Suboptimal
Responses to 3 Months of Imatinib Author: SaglioAbstract:
#PF405Poster Session: Chronic myeloid leukemia – ClinicalFriday,
June 14, 5:30-7 PM, Poster Area
- DASFREE: 2-Year Update: Dasatinib
Discontinuation in Patients (pts) with Chronic Myeloid Leukemia in
Chronic Phase (CML-CP) and Deep Molecular Response (DMR)
Author: ShahAbstract: #PF408Poster Session: Chronic myeloid
leukemia – ClinicalFriday, June 14, 5:30-7 PM, Poster Area
- Growth Rate and Endocrine Effects of
Dasatinib Therapy Observed in Retrospective Analysis of a Phase II
Clinical Trial for Pediatric Patients with Chronic Myeloid Leukemia
in Chronic Phase (CML-CP) Author: PattersonAbstract:
#PF416Poster Session: Chronic myeloid leukemia – ClinicalFriday,
June 14, 5:30-7 PM, Poster Area
- Dosing Patterns of Dasatinib and
Nilotinib Use in SIMPLICITY, an Observational Study in
Chronic-Phase Chronic Myeloid Leukemia (CP-CML) Patients (pts) in
Routine Clinical Practice Author: CortesAbstract: #PS1181Poster
Session: Chronic myeloid leukemia – ClinicalSaturday, June 15,
5:30-7 PM, Poster Area
Bristol-Myers Squibb: Advancing
Oncology Research
At Bristol-Myers Squibb, patients are at the center of
everything we do. The focus of our research is to increase quality,
long-term survival for patients and make cure a possibility.
Through a unique multidisciplinary approach powered by
translational science, we harness our deep scientific experience in
oncology and Immuno-Oncology (I-O) research to identify novel
treatments tailored to individual patient needs. Our researchers
are developing a diverse, purposefully built pipeline designed to
target different immune system pathways and address the complex and
specific interactions between the tumor, its microenvironment and
the immune system. We source innovation internally, and in
collaboration with academia, government, advocacy groups and
biotechnology companies, to help make the promise of
transformational medicines, like I-O, a reality for patients.
About 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
treated more than 35,000 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 65
countries, including the United States, the European Union, Japan
and China. 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 unresectable or metastatic melanoma.
OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab),
is indicated for the treatment of patients with unresectable or
metastatic melanoma.
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 metastatic small cell lung cancer (SCLC) with progression
after platinum-based chemotherapy and at least one other line of
therapy. 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 advanced renal cell carcinoma (RCC) who have received prior
anti-angiogenic therapy.
OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab),
is indicated for the treatment of patients with intermediate or
poor risk, previously untreated advanced renal cell carcinoma
(RCC).
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), as a single agent, 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), in combination with YERVOY® (ipilimumab),
is indicated for the treatment of adults and pediatric patients 12
years and older 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.
OPDIVO® (nivolumab) is indicated for the adjuvant treatment of
patients with melanoma with involvement of lymph nodes or
metastatic disease who have undergone complete resection.
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 1 mg/kg with YERVOY 3 mg/kg,
immune-mediated pneumonitis occurred in 6% (25/407) of
patients. In RCC patients receiving OPDIVO 3 mg/kg with YERVOY
1 mg/kg, immune-mediated pneumonitis occurred in 4.4% (24/547) of
patients. In MSI-H/dMMR mCRC patients receiving OPDIVO 3 mg/kg
with YERVOY 1 mg/kg, immune-mediated pneumonitis occurred in 1.7%
(2/119) 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 1 mg/kg with YERVOY 3
mg/kg, immune-mediated colitis occurred in 26% (107/407) of
patients including three fatal cases. In RCC patients
receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg, immune-mediated
colitis occurred in 10% (52/547) of patients. In MSI-H/dMMR
mCRC patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg,
immune-mediated colitis occurred in 7% (8/119) of patients.
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 1 mg/kg with YERVOY 3 mg/kg, immune-mediated hepatitis
occurred in 13% (51/407) of patients. In RCC patients
receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg, immune-mediated
hepatitis occurred in 7% (38/547) of patients. In MSI-H/dMMR
mCRC patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg,
immune-mediated hepatitis occurred in 8% (10/119) 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 1
mg/kg with YERVOY 3 mg/kg, hypophysitis occurred in 9% (36/407) of
patients. In RCC patients receiving OPDIVO 3 mg/kg with YERVOY
1 mg/kg, hypophysitis occurred in 4.6% (25/547) of
patients. In MSI-H/dMMR mCRC patients receiving OPDIVO 3 mg/kg
with YERVOY 1 mg/kg, immune-mediated hypophysitis occurred in 3.4%
(4/119) of patients. In patients receiving OPDIVO monotherapy,
adrenal insufficiency occurred in 1% (20/1994) of patients. In
patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg, adrenal
insufficiency occurred in 5% (21/407) of patients. In RCC
patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg, adrenal
insufficiency occurred in 7% (41/547) of patients. In
MSI-H/dMMR mCRC patients receiving OPDIVO 3 mg/kg with YERVOY 1
mg/kg, adrenal insufficiency occurred in 5.9% (7/119) 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 1 mg/kg with YERVOY 3 mg/kg,
hypothyroidism or thyroiditis resulting in hypothyroidism occurred
in 22% (89/407) of patients. Hyperthyroidism occurred in 8%
(34/407) of patients receiving this dose of OPDIVO with
YERVOY. In RCC patients receiving OPDIVO 3 mg/kg with YERVOY 1
mg/kg, hypothyroidism or thyroiditis resulting in hypothyroidism
occurred in 22% (119/547) of patients. Hyperthyroidism occurred in
12% (66/547) of patients receiving this dose of OPDIVO with
YERVOY. In MSI-H/dMMR mCRC patients receiving OPDIVO 3 mg/kg
with YERVOY 1 mg/kg, hypothyroidism or thyroiditis resulting in
hypothyroidism occurred in 15% (18/119) of patients.
Hyperthyroidism occurred in 12% (14/119) of patients. In
patients receiving OPDIVO monotherapy, diabetes occurred in 0.9%
(17/1994) of patients. In patients receiving OPDIVO 1 mg/kg
with YERVOY 3 mg/kg, diabetes occurred in 1.5% (6/407) of
patients. In RCC patients receiving OPDIVO 3 mg/kg with YERVOY
1 mg/kg, diabetes occurred in 2.7% (15/547) 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. Six 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 1 mg/kg with YERVOY 3
mg/kg, immune-mediated nephritis and renal dysfunction occurred in
2.2% (9/407) of patients. In RCC patients receiving OPDIVO 3
mg/kg with YERVOY 1 mg/kg, immune-mediated nephritis and renal
dysfunction occurred in 4.6% (25/547) of patients. In
MSI-H/dMMR mCRC patients receiving OPDIVO 3 mg/kg with YERVOY 1
mg/kg, immune-mediated nephritis and renal dysfunction occurred in
1.7% (2/119) 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 1 mg/kg
with YERVOY 3 mg/kg, immune-mediated rash occurred in 22.6%
(92/407) of patients. In RCC patients receiving OPDIVO 3 mg/kg
with YERVOY 1 mg/kg, immune-mediated rash occurred in 16.6%
(91/547) of patients. In MSI-H/dMMR mCRC patients receiving
OPDIVO 3 mg/kg with YERVOY 1 mg/kg, immune-mediated rash occurred
in 14% (17/119) 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 1 mg/kg with YERVOY 3 mg/kg (0.2%) after
1.7 months of exposure. Encephalitis occurred in one RCC
patient receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg (0.2%) after
approximately 4 months of exposure. Encephalitis occurred in
one MSI-H/dMMR mCRC patient (0.8%) receiving OPDIVO 3 mg/kg with
YERVOY 1 mg/kg after 15 days 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, aplastic anemia,
pericarditis, and myasthenic syndrome.
If uveitis occurs in combination with other immune-mediated
adverse reactions, consider a Vogt-Koyanagi-Harada-like syndrome,
which has been observed in patients receiving OPDIVO and may
require treatment with systemic steroids to reduce the risk of
permanent vision loss.
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 as a
60-minute infusion, infusion-related reactions occurred
in 6.4% (127/1994) of patients. In a separate study in which
patients received OPDIVO monotherapy as a 60-minute infusion or a
30-minute infusion, infusion-related reactions occurred in 2.2%
(8/368) and 2.7% (10/369) of patients, respectively. Additionally,
0.5% (2/368) and 1.4% (5/369) of patients, respectively,
experienced adverse reactions within 48 hours of infusion that led
to dose delay, permanent discontinuation or withholding of
OPDIVO. In patients receiving OPDIVO 1 mg/kg with YERVOY 3
mg/kg every 3 weeks, infusion-related reactions occurred
in 2.5% (10/407) of patients. In RCC patients
receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg, infusion-related
reactions occurred in 5.1% (28/547) of patients. In MSI-H/dMMR
mCRC patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg,
infusion-related reactions occurred in 4.2% (5/119) of
patients.
Complications of Allogeneic Hematopoietic Stem Cell
Transplantation
Fatal and other serious complications can occur in patients who
receive allogeneic hematopoietic stem cell transplantation (HSCT)
before or after being treated with a PD-1 receptor blocking
antibody. Transplant-related complications include hyperacute
graft-versus-host-disease (GVHD), acute GVHD, chronic GVHD, hepatic
veno-occlusive disease (VOD) after reduced intensity conditioning,
and steroid-requiring febrile syndrome (without an identified
infectious cause). These complications may occur despite
intervening therapy between PD-1 blockade and allogeneic HSCT.
Follow patients closely for evidence of transplant-related
complications and intervene promptly. Consider the benefit versus
risks of treatment with a PD-1 receptor blocking antibody prior to
or after an allogeneic HSCT.
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.
Increased Mortality in Patients with Multiple Myeloma when
OPDIVO is Added to a Thalidomide Analogue and Dexamethasone
In clinical trials in patients with multiple myeloma, the
addition of OPDIVO to a thalidomide analogue plus dexamethasone
resulted in increased mortality. Treatment of patients with
multiple myeloma with a PD-1 or PD-L1 blocking antibody in
combination with a thalidomide analogue plus dexamethasone is not
recommended outside of controlled clinical trials.
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 breastfeeding 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 (74%
and 44%), adverse reactions leading to permanent discontinuation
(47% and 18%) or to dosing delays (58% and 36%), and Grade 3 or 4
adverse reactions (72% and 51%) 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 2.2%), colitis (10% and 1.9%), and pyrexia (10% and
1.0%). 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 ≥2% of patients
receiving OPDIVO were pneumonia, pulmonary embolism, dyspnea,
pyrexia, pleural effusion, pneumonitis, and respiratory
failure. In Checkmate 032, serious adverse reactions occurred
in 45% of patients receiving OPDIVO (n=245). The most frequent
serious adverse reactions reported in at least 2% of patients
receiving OPDIVO were pneumonia, dyspnea, pneumonitis, pleural
effusions, and dehydration. 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 214, serious adverse reactions
occurred in 59% of patients receiving OPDIVO plus YERVOY and in 43%
of patients receiving sunitinib. The most frequent serious adverse
reactions reported in ≥2% of patients were diarrhea, pyrexia,
pneumonia, pneumonitis, hypophysitis, acute kidney injury, dyspnea,
adrenal insufficiency, and colitis; in patients treated with
sunitinib, they were pneumonia, pleural effusion, and
dyspnea. 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 (n=236). The most frequent serious
adverse reactions reported in ≥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 ≥2% of patients
receiving OPDIVO were urinary tract infection, sepsis, diarrhea,
small intestine obstruction, and general physical health
deterioration. In Checkmate 142 in MSI-H/dMMR mCRC patients
receiving OPDIVO with YERVOY, serious adverse reactions occurred in
47% of patients. The most frequent serious adverse reactions
reported in ≥2% of patients were colitis/diarrhea, hepatic events,
abdominal pain, acute kidney injury, pyrexia, and
dehydration. In Checkmate 040, serious adverse reactions
occurred in 49% of patients (n=154). The most frequent serious
adverse reactions reported in ≥2% of patients were pyrexia,
ascites, back pain, general physical health deterioration,
abdominal pain, and pneumonia. In Checkmate 238, Grade 3 or 4
adverse reactions occurred in 25% of OPDIVO-treated patients
(n=452). The most frequent Grade 3 and 4 adverse reactions reported
in ≥2% of OPDIVO-treated patients were diarrhea and increased
lipase and amylase. Serious adverse reactions occurred in 18% of
OPDIVO-treated patients.
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 (62%), diarrhea (54%),
rash (53%), nausea (44%), pyrexia (40%), pruritus (39%),
musculoskeletal pain (32%), vomiting (31%), decreased appetite
(29%), cough (27%), headache (26%), dyspnea (24%), upper
respiratory tract infection (23%), arthralgia (21%), and increased
transaminases (25%). In Checkmate 067, the most common (≥20%)
adverse reactions in the OPDIVO arm (n=313) were fatigue (59%),
rash (40%), musculoskeletal pain (42%), diarrhea (36%), nausea
(30%), cough (28%), pruritus (27%), upper respiratory tract
infection (22%), decreased appetite (22%), headache (22%),
constipation (21%), arthralgia (21%), and vomiting (20%). 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
032, the most common adverse reactions (≥20%) in patients receiving
OPDIVO (n=245) were fatigue (45%), decreased appetite (27%),
musculoskeletal pain (25%), dyspnea (22%), nausea (22%), diarrhea
(21%), constipation (20%), and cough (20%). In Checkmate 025,
the most common adverse reactions (≥20%) reported in patients
receiving OPDIVO (n=406) vs everolimus (n=397) were fatigue (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 214, the most common
adverse reactions (≥20%) reported in patients treated with OPDIVO
plus YERVOY (n=547) vs sunitinib (n=535) were fatigue (58% vs 69%),
rash (39% vs 25%), diarrhea (38% vs 58%), musculoskeletal pain (37%
vs 40%), pruritus (33% vs 11%), nausea (30% vs 43%), cough (28% vs
25%), pyrexia (25% vs 17%), arthralgia (23% vs 16%), decreased
appetite (21% vs 29%), dyspnea (20% vs 21%), and vomiting (20% vs
28%). 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 (n=236) 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 142 in
MSI-H/dMMR mCRC patients receiving OPDIVO as a single agent, the
most common adverse reactions (≥20%) were fatigue (54%), diarrhea
(43%), abdominal pain (34%), nausea (34%), vomiting (28%),
musculoskeletal pain (28%), cough (26%), pyrexia (24%), rash (23%),
constipation (20%), and upper respiratory tract infection
(20%). In Checkmate 142 in MSI-H/dMMR mCRC patients receiving
OPDIVO with YERVOY, the most common adverse reactions (≥20%) were
fatigue (49%), diarrhea (45%), pyrexia (36%), musculoskeletal pain
(36%), abdominal pain (30%), pruritus (28%), nausea (26%), rash
(25%), decreased appetite (20%), and vomiting (20%). 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%). In Checkmate
238, the most common adverse reactions (≥20%) reported in
OPDIVO-treated patients (n=452) vs ipilimumab-treated patients
(n=453) were fatigue (57% vs 55%), diarrhea (37% vs 55%), rash (35%
vs 47%), musculoskeletal pain (32% vs 27%), pruritus (28% vs 37%),
headache (23% vs 31%), nausea (23% vs 28%), upper respiratory
infection (22% vs 15%), and abdominal pain (21% vs 23%). The most
common immune-mediated adverse reactions were rash (16%),
diarrhea/colitis (6%), and hepatitis (3%).
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 for OPDIVO
and YERVOY, including Boxed WARNING regarding
immune-mediated adverse reactions for YERVOY.
Checkmate Trials and Patient Populations
Checkmate 037–previously treated metastatic melanoma;
Checkmate 066–previously untreated metastatic melanoma;
Checkmate 067–previously untreated metastatic melanoma, as a
single agent or in combination with YERVOY; Checkmate
017–second-line treatment of metastatic squamous non-small cell
lung cancer; Checkmate 057–second-line treatment of
metastatic non-squamous non-small cell lung cancer; Checkmate
032–small cell lung cancer; Checkmate 025–previously
treated renal cell carcinoma; Checkmate 214–previously
untreated renal cell carcinoma, in combination with YERVOY;
Checkmate 205/039–classical Hodgkin lymphoma; Checkmate
141–recurrent or metastatic squamous cell carcinoma of the head
and neck; Checkmate 275–urothelial carcinoma; Checkmate
142–MSI-H or dMMR metastatic colorectal cancer, as a single
agent or in combination with YERVOY; Checkmate
040–hepatocellular carcinoma; Checkmate 238–adjuvant
treatment of melanoma.
About Empliciti
Empliciti is an immunostimulatory antibody that
specifically targets Signaling Lymphocyte Activation Molecule
Family member 7 (SLAMF7), a cell-surface glycoprotein. SLAMF7 is
expressed on myeloma cells independent of cytogenetic
abnormalities. SLAMF7 also is expressed on Natural Killer cells,
plasma cells and at lower levels on specific immune cell subsets of
differentiated cells within the hematopoietic lineage.
Empliciti has a dual mechanism-of-action. It directly
activates the immune system through Natural Killer cells via the
SLAMF7 pathway. Empliciti also targets SLAMF7 on myeloma
cells, tagging these malignant cells for Natural Killer
cell-mediated destruction via antibody-dependent cellular
toxicity.
Empliciti was initially approved by the FDA in 2015 in
combination with lenalidomide and dexamethasone for the treatment
of patients with multiple myeloma who have received one to three
prior therapies.
U.S. FDA-APPROVED INDICATIONS FOR
EMPLICITI®
EMPLICITI® (elotuzumab) is indicated in combination with
lenalidomide and dexamethasone for the treatment of adult patients
with multiple myeloma who have received one to three prior
therapies.
EMPLICITI® (elotuzumab) is indicated in combination with
pomalidomide and dexamethasone for the treatment of adult patients
with multiple myeloma who have received at least two prior
therapies including lenalidomide and a proteasome inhibitor.
IMPORTANT SAFETY INFORMATION
Infusion Reactions
Infusion reactions were reported in 10% of patients treated with
EMPLICITI in the ELOQUENT-2 trial [EMPLICITI + lenalidomide +
dexamethasone (ERd) vs lenalidomide + dexamethasone (Rd)] and 3.3%
in the ELOQUENT-3 trial [EMPLICITI + pomalidomide + dexamethasone
(EPd) vs pomalidomide + dexamethasone (Pd)].
In the ELOQUENT-2 trial, all infusion reactions were Grade 3 or
lower, with Grade 3 infusion reactions occurring in 1% of patients.
The most common symptoms included fever, chills, and hypertension.
Bradycardia and hypotension also developed during infusions. In the
trial, 5% of patients required interruption of the administration
of EMPLICITI for a median of 25 minutes due to infusion reactions,
and 1% of patients discontinued due to infusion reactions. Of the
patients who experienced an infusion reaction, 70% (23/33) had them
during the first dose.
In the ELOQUENT-3 trial, the only infusion reaction symptom was
chest discomfort (2%), which was Grade 1. All the patients who
experienced an infusion reaction had them during the first
treatment cycle.
If a Grade 2 or higher infusion reaction occurs, interrupt the
EMPLICITI infusion and institute appropriate medical and supportive
measures. If the infusion reaction recurs, stop the EMPLICITI
infusion and do not restart it on that day. Severe infusion
reactions may require permanent discontinuation of EMPLICITI
therapy and emergency treatment.
Premedicate with dexamethasone, H1 blocker, H2 blocker, and
acetaminophen prior to EMPLICITI infusion.
Infections
In the ELOQUENT-2 trial (N=635), infections were reported in 81%
of patients in the ERd arm and 74% in the Rd arm. Grade 3-4
infections were 28% (ERd) and 24% (Rd). Discontinuations due to
infections were 3.5% (ERd) and 4.1% (Rd). Fatal infections were
2.5% (ERd) and 2.2% (Rd). Opportunistic infections were reported in
22% (ERd) and 13% (Rd). Fungal infections were 10% (ERd) and 5%
(Rd). Herpes zoster was 14% (ERd) and 7% (Rd).
In the ELOQUENT-3 trial (N=115), infections were reported in 65%
of patients in both the EPd arm and the Pd arm. Grade 3-4
infections were reported in 13% (EPd) and 22% (Pd).
Discontinuations due to infections were 7% (EPd) and 5% (Pd). Fatal
infections were 5% (EPd) and 3.6% (Pd). Opportunistic infections
were reported in 10% (EPd) and 9% (Pd). Herpes zoster was reported
in 5% (EPd) and 1.8% (Pd).
Monitor patients for development of infections and treat
promptly.
Second Primary Malignancies
In the ELOQUENT-2 trial (N=635), invasive second primary
malignancies (SPM) were 9% (ERd) and 6% (Rd). The rate of
hematologic malignancies was the same between ERd and Rd treatment
arms (1.6%). Solid tumors were reported in 3.5% (ERd) and 2.2%
(Rd). Skin cancer was reported in 4.4% (ERd) and 2.8% (Rd).
In the ELOQUENT-3 trial (N=115), invasive SPMs were 0% (EPd) and
1.8% (Pd).
Monitor patients for the development of SPMs.
Hepatotoxicity
In the ELOQUENT-2 trial (N=635), AST/ALT >3X the upper limit,
total bilirubin >2X the upper limit, and alkaline phosphatase
<2X the upper limit were 2.5% (ERd) vs 0.6% (Rd). Of 8 patients
experiencing hepatotoxicity, 2 patients discontinued treatment
while 6 patients had resolution and continued. Monitor liver
enzymes periodically. Stop EMPLICITI upon ≥Grade 3 elevation of
liver enzymes. Continuation of treatment may be considered after
return to baseline values.
Interference with Determination of Complete Response
EMPLICITI is a humanized IgG kappa monoclonal antibody that can
be detected on both the serum protein electrophoresis and
immunofixation assays used for the clinical monitoring of
endogenous M-protein. This interference can impact the
determination of complete response and possibly relapse from
complete response in patients with IgG kappa myeloma protein.
Pregnancy/Females and Males of Reproductive Potential
There are no available data on EMPLICITI use in pregnant women
to inform a drug-associated risk of major birth defects and
miscarriage.
There is a risk of fetal harm, including severe life-threatening
human birth defects, associated with lenalidomide and pomalidomide,
and they are contraindicated for use in pregnancy. Refer to the
respective product full prescribing information for requirements
regarding contraception and the prohibitions against blood and/or
sperm donation due to presence and transmission in blood and/or
semen and for additional information.
Adverse Reactions
ELOQUENT-2 trial:
- Serious adverse reactions were 65%
(ERd) and 57% (Rd). The most frequent serious adverse reactions in
the ERd arm compared to the Rd arm were: pneumonia (15%, 11%),
pyrexia (7%, 5%), respiratory tract infection (3.1%, 1.3%), anemia
(2.8%, 1.9%), pulmonary embolism (3.1%, 2.5%), and acute renal
failure (2.5%, 1.9%).
- The most common adverse reactions in
ERd and Rd, respectively (≥20%) were fatigue (62%, 52%), diarrhea
(47%, 36%), pyrexia (37%, 25%), constipation (36%, 27%), cough
(34%, 19%), peripheral neuropathy (27%, 21%), nasopharyngitis (25%,
19%), upper respiratory tract infection (23%, 17%), decreased
appetite (21%, 13%), and pneumonia (20%, 14%).
ELOQUENT-3 trial:
- Serious adverse reactions were 22%
(EPd) and 15% (Pd). The most frequent serious adverse reactions in
the EPd arm compared to the Pd arm were: pneumonia (13%, 11%) and
respiratory tract infection (7%, 3.6%).
- The most common adverse reactions in
EPd arm (≥20% EPd) and Pd, respectively, were constipation (22%,
11%) and hyperglycemia (20%, 15%).
Please see the full Prescribing
Information.
About Sprycel
Sprycel is a second-generation tyrosine kinase inhibitor (TKI)
designed to help inhibit BCR-ABL, an abnormal protein found on the
mutated Philadelphia chromosome in most patients with chronic
myeloid leukemia (CML) and some patients with ALL, which can
trigger the overproduction of damaged or immature white blood
cells. By targeting the BCR-ABL protein, Sprycel can reduce the
number of damaged white blood cells in the body, allowing for the
production of more normal cells.
Sprycel is currently approved in more than 60 countries for the
treatment of adults with Ph+ ALL or Ph+ CML in chronic phase
(CP-CML) who are resistant or intolerant to prior therapy, and in
more than 50 countries for the treatment of adults with newly
diagnosed Ph+ CP-CML. In 2017, Sprycel received its first pediatric
indication when it became the first second-generation TKI approved
for the treatment of patients one year of age and older with Ph+
CP-CML. Sprycel is also approved in combination with chemotherapy
for the treatment of pediatric patients with newly diagnosed Ph+
ALL.
In Europe, both pediatric indications for Sprycel include the
PFOS formulation, the approvals of which made Sprycel the first TKI
with an approved powder formulation for administration in pediatric
patients with Ph+ CP-CML and Ph+ ALL. The PFOS formulation is also
approved for adult patients with Ph+ CP-CML who cannot swallow
tablets.
U.S. FDA-APPROVED INDICATIONS FOR
SPRYCEL®
SPRYCEL® (dasatinib) is indicated for the treatment of adult
patients with:
- Newly diagnosed 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
SPRYCEL® is indicated for the treatment of pediatric patients 1
year of age and older with:
- Ph+ CML in chronic phase
- Newly diagnosed Ph+ ALL in combination
with chemotherapy
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
- In pediatric patients with Ph+ ALL
treated with SPRYCEL in combination with chemotherapy, perform CBCs
prior to the start of each block of chemotherapy and as clinically
indicated. During the consolidation blocks of chemotherapy, perform
CBCs every 2 days until recovery
- 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.
Monitor bone growth and development in pediatric patients.
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:
Effect of Other Drugs on Dasatinib
- 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 administered as
single-agent therapy 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 all 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 a multicohort study of SPRYCEL administered continuously in
combination with multiagent chemotherapy in 81 pediatric patients
with newly diagnosed Ph+ ALL, the median duration of therapy was 24
months (range 2 to 27 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 patients, 88% of
patients experienced adverse reactions at some time and 19%
experienced adverse reactions leading to treatment
discontinuation.
Among the 1618 adult 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 adult 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 CML 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
- Adverse reactions associated with bone
growth and development were reported in 5 (5.2%) pediatric patients
with chronic phase CML
- In the pediatric studies, the rates of
laboratory abnormalities were consistent with the known profile for
laboratory parameters in adults
- In pediatric subjects with Ph+ ALL who
were administered SPRYCEL in combination with multiagent
chemotherapy
- Fatal adverse reactions occurred in 3
patients (4%), all of which were due to infections
- Eight patients (10%) experienced
adverse reactions leading to treatment discontinuation
- The most common serious adverse
reactions (incidence ≥10%) were pyrexia, febrile neutropenia,
mucositis, diarrhea, sepsis, hypotension, infections (bacterial,
viral and fungal), hypersensitivity, vomiting, renal insufficiency,
abdominal pain, and musculoskeletal pain
- Grade 3/4 laboratory abnormalities
(≥10%) included neutropenia (96%), thrombocytopenia (88%), anemia
(82%), elevated SGPT (ALT) (47%), hypokalemia (40%), elevated SGOT
(AST) (26%), hypocalcemia (19%), hyponatremia (19%), elevated
bilirubin (11%), and hypophosphatemia (11%)
Most common adverse reactions (≥15%) in patients receiving
SPRYCEL as single-agent therapy included myelosuppression, fluid
retention events, diarrhea, headache, skin rash, hemorrhage,
dyspnea, fatigue, nausea, and musculoskeletal pain.
Most common adverse reactions (≥30%) in pediatric patients
receiving SPRYCEL in combination with chemotherapy included
mucositis, febrile neutropenia, pyrexia, diarrhea, nausea,
vomiting, musculoskeletal pain, abdominal pain, cough, headache,
rash, fatigue, constipation, arrhythmia, hypertension, edema,
infections (bacterial, viral and fungal), hypotension, decreased
appetite, hypersensitivity, dyspnea, epistaxis, peripheral
neuropathy, and altered state of consciousness.
Please see full Prescribing Information.
About the Bristol-Myers Squibb and Ono
Pharmaceutical Collaboration
In 2011, through a collaboration agreement with Ono
Pharmaceutical Co., 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, Ono and Bristol-Myers
Squibb 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
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the meaning of the Private Securities Litigation Reform Act of 1995
regarding the research, development and commercialization of
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statements. Such forward-looking statements are based on historical
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future financial results, goals, plans and objectives and involve
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or external factors that could delay, divert or change any of them
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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, 2018, as updated by our subsequent Quarterly
Reports on Form 10-Q, Current Reports on Form 8-K and other filings
with the Securities and Exchange Commission. The forward-looking
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securities law, Bristol-Myers Squibb undertakes no obligation to
publicly update or revise any forward-looking statement, whether as
a result of new information, future events, changed circumstances
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Bristol-Myers Squibb CompanyMedia Inquiries:Ken
Dominski609-302-3114ken.dominski@bms.com
Investors:Tim Power609-252-7509timothy.power@bms.com
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