Long-term survival data for a broad set of
tumor types including advanced non-small and small cell lung
cancer, advanced melanoma, and up to 5-year follow up in renal cell
carcinoma, to be presented
Broad data set for the Opdivo and
Yervoy combination in several tumors, including first-line
non-small cell lung cancer, recurrent glioblastoma multiforme, and
MSI-high metastatic colorectal cancer, to be presented
Data across 13 types of cancers, including
first time presentations in advanced bladder and MSI-high
metastatic colorectal cancers, and new research in classical
Hodgkin lymphoma, for which Opdivo was recently approved in
the U.S.
Bristol-Myers Squibb Company (NYSE:BMY) announced today 36
presentations, including seven oral presentations and eight poster
discussions, highlighting data from studies evaluating Opdivo®
(nivolumab), Yervoy® (ipilimumab), Empliciti™ (elotuzumab) and
Sprycel® (dasatinib), across 13 types of cancers, will be featured
at the 2016 American Society of Clinical Oncology (ASCO) Annual
Meeting in Chicago, IL from June 3-7. The data presented at this
meeting builds on the Company’s understanding of the clinical
profile of these agents – as monotherapy or in combination – and
reinforce its commitment to addressing significant unmet patient
needs in a wide range of solid tumors and blood cancers.
Jean Viallet, M.D., Global Clinical Research Lead, Oncology,
Bristol-Myers Squibb, commented, “Our Immuno-Oncology research goal
is centered around increasing quality long-term survival – and
doing so through the use of Immuno-Oncology combination regimens.
Our development program has led to the introduction of several
treatment options for cancers such as metastatic melanoma,
previously treated advanced lung, renal cell carcinoma, multiple
myeloma, and classical Hodgkin lymphoma, and through our robust
research pipeline we continue to evaluate the potential of
Immuno-Oncology in additional tumor types. At this year’s ASCO, we
look forward to sharing research from our ongoing clinical trials
evaluating our medicines - as monotherapy or in combination - in
several types of difficult-to-treat cancers.”
The key data presentations, including clinical science symposia
and oral presentations, are:
- CheckMate -012: New overall
survival data evaluating the Opdivo and Yervoy combination in
first-line advanced non-small cell lung
cancer (Abstract #3001). Data will be presented during an
oral abstract session on Saturday, June 4, 1:27 PM – 1:39 PM
CDT.
- CheckMate -032: New overall
survival data from a phase 1/2 trial evaluating Opdivo as
monotherapy and in combination with Yervoy in patients with
advanced small cell lung cancer
(Abstract #100). Data from CheckMate -032 will be presented during
a Clinical Science Symposium on Saturday, June 4, 2016, 8:12 AM –
8:24 AM CDT.
- CheckMate -067: Updated results
from pivotal, phase 3 trial of Opdivo in combination with Yervoy in
treatment-naive patients with advanced melanoma (Abstract #9505). Data will be
presented during an oral abstract session on Monday, June 6, 2:39
PM – 2:51 PM CDT.
- Study -010/-003: Long-term
overall survival with Opdivo in previously treated patients with
advanced renal cell carcinoma from
phase 1 and 2 studies (Abstract #4507). Data will be presented
during an oral abstract session on Sunday, June 5, 10:24 AM – 10:36
AM CDT.
- CheckMate -141: Updated phase 3
data evaluating Opdivo versus investigator’s choice for recurrent
or metastatic head and neck squamous cell
carcinoma, including quality of life assessments (Abstract
#6009). Data will be presented during a Clinical Science Symposium
on Monday, June 6, 11:30 AM – 11:42 AM CDT.
- CheckMate -032: First
presentation of clinical results from phase 1/2 trial evaluating
Opdivo in metastatic urothelial
cancer in previously treated patients (Abstract #4501). Data
will be presented during an oral abstract session on Sunday, June
5, 8:12 AM – 8:24 AM CDT.
- CheckMate -142: First disclosure
of clinical results of the Opdivo and Yervoy combination regimen in
patients with metastatic colorectal
cancer with and without high microsatellite instability
(Abstract #3501). Data will be presented during an oral abstract
session on Sunday, June 5, 8:12 AM – 8:24 AM CDT.
The full set of data to be presented by Bristol-Myers Squibb
includes:
Bladder
- Efficacy and safety of nivolumab
monotherapy in metastatic urothelial cancer: Results from the phase
1/2 CheckMate -032 studyAuthor: P. SharmaAbstract #4501Oral
Abstract Session, Genitourinary (Nonprostate) CancerSunday, June 5,
2016, 8:12 AM – 8:24 AM CDT, Hall D2
Chronic Myeloid Leukemia
- Achievement of early molecular
response in patients with chronic myeloid leukemia in chronic phase
treated with dasatinib or imatinib from DASISIONAuthor: N.
ShahAbstract #7055, Poster Board #47Poster Session, Hematologic
Malignancies – Leukemia, Myelodysplastic Syndromes, and
AllotransplateMonday, June 6, 2016, 8:00 AM – 11:30 AM CDT, Hall
A
Colorectal
- Nivolumab ± ipilimumab in
treatment of patients with metastatic colorectal cancer with and
without high microsatellite instability: CheckMate -142 interim
resultsAuthor: M. OvermanAbstract #3501Oral Abstract Session,
Gastrointestinal (Colorectal) CancerSunday, June 5, 2016, 8:12 AM –
8:24 AM CDT, Hall B1
Esophageal / Gastric
- A randomized, open-label, two-arm
phase 2 trial comparing the efficacy of sequential ipilimumab
versus best supportive care following first-line chemotherapy in
patients with unresectable, locally advanced/metastatic gastric or
gastro-esophageal junction cancerAuthor: M. MoehlerAbstract
#4011, Poster Board #3Poster Discussion Session, Gastrointestinal
(Noncolorectal) CancerSaturday, June 4, 2016, 3:00 PM – 4:15 PM
CDT, Hall D1
- CheckMate -032: Phase 1/2,
open-label study of safety and activity of nivolumab alone or with
ipilimumab in advanced and metastatic gastric cancerAuthor: Y.
Y. JanjigianAbstract #4010, Poster Board #2Poster Discussion
Session, Gastrointestinal (Noncolorectal) CancerSaturday, June 4,
2016, 3:00 PM – 4:15 PM CDT, Hall D1
Glioblastoma
- A randomized, phase 3, open-label
study of nivolumab versus temozolomide in combination with
radiotherapy in adult patients with newly diagnosed,
O-6-methylguanine DNA methyltransferase (MGMT)-unmethylated
glioblastoma [CheckMate -498]Author: J. SampsonAbstract
#TPS2079, Poster Board #265bPoster Session, Central Nervous System
TumorsSaturday, June 4, 2016, 1:00 PM – 4:30 PM CDT, Hall A
- Safety and activity of nivolumab
monotherapy and nivolumab in combination with ipilimumab in
recurrent glioblastoma: Updated results from CheckMate
-143Author: D. A. ReardonAbstract #2014, Poster Board
#203Poster Discussion Session, Central Nervous System
TumorsSaturday, June 4, 2016, 4:45 PM – 6:00 PM CDT, S102
Head and Neck
- Further evaluations of nivolumab
versus investigator’s choice chemotherapy for recurrent or
metastatic squamous cell carcinoma of the head and neck: CheckMate
-141Author: R. FerrisAbstract #6009Clinical Science Symposium,
Harnessing the Immune System in Head and Neck Cancer: Evolving
Standards in Metastatic DiseaseMonday, June 6, 2016, 11:30 AM –
11:42 AM CDT, S100bc
Hepatocellular Carcinoma
- Safety and antitumor activity of
nivolumab in patients with advanced hepatocellular carcinoma:
Interim analysis of dose-expansion cohorts from the phase 1/2
CheckMate -040 studyAuthor: B. SangroAbstract #4078, Poster
Board #70Poster Session, Gastrointestinal (Noncolorectal)
CancerSaturday, June 4, 2016, 8:00 AM – 11:30 AM CDT, Hall A
- A randomized, multicenter, phase 3
study of nivolumab vs sorafenib as first-line treatment in patients
with advanced hepatocellular carcinoma: CheckMate -459Author:
B. SangroAbstract #TPS4147, Poster Board #131aPoster Session,
Gastrointestinal (Noncolorectal) CancerSaturday, June 4, 2016, 8:00
AM – 11:30 AM CDT, Hall A
- Phase 1/2 safety and antitumor
activity of nivolumab in patients with advanced hepatocellular
carcinoma: Interim analysis of the CheckMate -040 dose escalation
studyAuthor: A. B. El-KhoueiryAbstract #4012, Poster Board
#4Poster Discussion Session, Gastrointestinal (Noncolorectal)
CancerSaturday, June 4, 2016, 3:00 PM – 4:15 PM CDT, Hall D1
Lung
- CheckMate -032: Nivolumab alone or
in combination with ipilimumab for the treatment of recurrent small
cell lung cancerAuthor: S. AntoniaAbstract #100Clinical Science
Symposium, The View Beyond Single-Agent Checkpoint
BlockadeSaturday, June 4, 2016, 8:12 AM – 8:24 AM CDT, Hall D1
- Nivolumab versus docetaxel in
patients with advanced NSCLC: CheckMate -017/-057 2-year update and
exploratory cytokine profile analysesAuthor: H.
BorghaeiAbstract #9025, Poster Board #348Poster Session, Lung
Cancer—Non-Small Cell MetastaticSaturday, June 4, 2016, 8:00 AM –
11:30 AM CDT, Hall A
- Nivolumab in patients with advanced
non-small cell lung cancer and central nervous system
metastasesAuthor: J. GoldmanAbstract #9038, Poster Board
#361Poster Session, Lung Cancer—Non-Small Cell MetastaticSaturday,
June 4, 2016, 8:00 AM – 11:30 AM CDT, Hall A
- Lung Cancer Symptom Scale as a
marker of treatment benefit with nivolumab versus docetaxel in
patients with advanced non-squamous non-small cell lung cancer from
CheckMate -057Author: R. GrallaAbstract #9031, Poster Board
#354Poster Session, Lung Cancer—Non-Small Cell MetastaticSaturday,
June 4, 2016, 8:00 AM – 11:30 AM CDT, Hall A
- Estimated costs of managing
treatment-related adverse events of nivolumab and docetaxel in the
CheckMate -017 and CheckMate -057 phase 3 non-small cell lung
cancer trialsAuthor: M. VenkatachalamAbstract #6617, Poster
Board #100Poster Session, Health Services Research and Quality of
CareSaturday, June 4, 2016, 1:00 PM – 4:30 PM CDT, Hall A
- CheckMate -331: An open-label,
randomized phase 3 trial of nivolumab versus chemotherapy in
patients with relapsed small cell lung cancer after first-line
platinum-based chemotherapyAuthor: L. HornAbstract #TPS8578,
Poster Board #202aPoster Session, Lung Cancer—Non-Small Cell
Local-Regional/Small Cell/Other Thoracic CancersSaturday, June 4,
2016, 8:00 AM – 11:30 AM CDT, Hall A
- CheckMate -451: A randomized,
double-blind, phase 3 trial of nivolumab, nivolumab plus
ipilimumab, or placebo as maintenance therapy in patients with
extensive-stage disease small cell lung cancer after first-line
platinum-based doublet chemotherapyAuthor: N. ReadyAbstract
#TPS8579, Poster Board #202bPoster Session, Lung Cancer—Non-Small
Cell Local-Regional/Small Cell/Other Thoracic CancersSaturday, June
4, 2016, 8:00 AM – 11:30 AM CDT, Hall A
- Safety profile of nivolumab
administered as 30-minute infusion: Analysis of data from CheckMate
-153Author: D. WaterhouseAbstract #3059, Poster Board
#381Poster Session, Developmental Therapeutics—ImmunotherapySunday,
June 5, 2016, 8:00 AM – 11:30 AM CDT, Hall A
- CheckMate -012: Safety and efficacy
of first‐line nivolumab and ipilimumab in advanced non-small cell
lung cancerAuthor: M. HellmannAbstract #3001Oral Abstract
Session, Developmental Therapeutics—ImmunotherapySaturday, June 4,
2016, 1:27 PM – 1:39 PM CDT, Hall B1
Lymphoma (Hodgkin and
non-Hodgkin)
- Checkmate -205: Nivolumab in
classical Hodgkin lymphoma after autologous stem cell transplant
and brentuximab vedotin—A phase 2 studyAuthor: A.
YounesAbstract #7535, Poster Board #91Poster Discussion Session,
Hematologic Malignancies—Lymphoma and Chronic Lymphocytic
LeukemiaMonday, June 6, 2016, 1:15 PM – 2:45 PM CDT, E354b
- A phase 2 study of a
nivolumab–containing regimen in patients with newly diagnosed
classical Hodgkin lymphoma (Study 205 Cohort D)Author: P.
ArmandAbstract #TPS7573, Poster Board #128bPoster Session,
Hematologic Malignancies—Lymphoma and Chronic Lymphocytic
LeukemiaMonday, June 6, 2016, 8:00 AM – 11:30 AM CDT, Hall A
- A phase 1/2 study to evaluate safety
and efficacy of nivolumab plus brentuximab vedotin in patients with
CD30-expressing relapsed/refractory non-Hodgkin
lymphomasAuthor: P. ArmandAbstract #TPS7576, Poster Board
#130aPoster Session, Hematologic Malignancies—Lymphoma and Chronic
Lymphocytic LeukemiaMonday, June 6, 2016, 8:00 AM – 11:30 AM CDT,
Hall A
Melanoma
- Safety data from an expanded access
program of nivolumab in combination with ipilimumab in patients
with advanced melanomaAuthor: P. ChapmanAbstract #9525, Poster
Board #130Poster Session, Melanoma/Skin CancersSaturday, June 4,
2016, 1:00 PM – 4:30 PM CDT, Hall A
- Real-world overall survival in
advanced melanoma from the IMAGE studyAuthor: M.
MiddletonAbstract #9531, Poster Board #136Poster Session,
Melanoma/Skin CancersSaturday, June 4, 2016, 1:00 PM – 4:30 PM CDT,
Hall A
- Overall survival in patients with
advanced melanoma who discontinued treatment with nivolumab plus
ipilimumab due to toxicity in a phase 2 trial (CheckMate
-069)Author: F. S. HodiAbstract #9518, Poster Board #123Poster
Discussion Session, Melanoma/Skin CancersSaturday, June 4, 2016,
4:45 PM – 6:00 PM CDT, E354b
- Survival outcomes of nivolumab given
sequentially with ipilimumab in patients with advanced melanoma
(CheckMate -064)Author: J. WeberAbstract #9517, Poster Board
#122Poster Discussion Session, Melanoma/Skin CancersSaturday, June
4, 2016, 4:45 PM – 6:00 PM CDT, E354b
- Nivolumab safety in patients with
advanced melanoma who have progressed on or after ipilimumab: a
single-arm, open-label, multicenter, phase 2 study (CheckMate
-172)Author: P. AsciertoAbstract #9526, Poster Board #131Poster
Session, Melanoma/Skin CancersSaturday, June 4, 2016, 1:00 PM –
4:30 PM CDT, Hall A
- Updated results from a phase 3 trial
of nivolumab combined with ipilimumab in treatment-naive patients
with advanced melanoma (CheckMate -067)Author: J.
WolchokAbstract #9505Oral Abstract Session, Melanoma/Skin
CancersMonday, June 6, 2016, 2:39 PM - 2:51 PM CDT, Arie Crown
Theater
Multiple Myeloma
- Health care resource utilization in
relapsed/refractory multiple myeloma: Results from
PREAMBLEAuthor: H. GoldschmidtAbstract #6621, Poster Board
#104Poster Session, Health Services Research and Quality of
CareSaturday, June 4, 2016, 1:00 PM – 4:30 PM CDT, Hall A
- ELOQUENT-2 update: Phase 3 study of
elotuzumab plus lenalidomide/dexamethasone versus
lenalidomide/dexamethasone in relapsed/refractory multiple myeloma
– Identifying responders by subset analysisAuthor: S.
LonialAbstract #8037, Poster Board #302Poster Session, Hematologic
Malignancies—Plasma Cell DyscrasiaMonday, June 6, 2016, 8:00 AM –
11:30 AM CDT, Hall A
- A randomized phase 2 study of
pomalidomide/dexamethasone with or without elotuzumab in patients
with relapsed/refractory multiple myelomaAuthor: J. San
MiguelAbstract #TPS8066, Poster Board #331aPoster Session,
Hematologic Malignancies—Plasma Cell DyscrasiaMonday, June 6, 2016,
8:00 AM – 11:30 AM CDT, Hall A
Renal Cell Carcinoma
- Long-term overall survival with
nivolumab in previously treated patients with advanced renal cell
carcinoma from phase 1 and 2 studiesAuthor: D.
McDermottAbstract #4507Oral Abstract Session, Genitourinary
(Nonprostate) CancerSunday, June 5, 2016, 10:24 AM – 10:36 AM CDT,
Hall D2
- Correlation of response with overall
survival for nivolumab versus everolimus in advanced renal cell
carcinoma: Results from the phase 3 CheckMate -025 studyAuthor:
R. MotzerAbstract #4552, Poster Board #174Poster Session,
Genitourinary (Nonprostate) CancerMonday, June 6, 2016, 1:00 PM –
4:30 PM CDT, Hall A
- Quality of life and overall survival
in patients with advanced clear-cell renal cell carcinoma treated
with nivolumab versus everolimus in the phase 3 CheckMate -025
studyAuthor: D. CellaAbstract #4549, Poster Board #171Poster
Session, Genitourinary (Nonprostate) CancerMonday, June 6, 2016,
1:00 PM – 4:30 PM CDT, Hall A
- Treatment beyond progression with
nivolumab in patients with advanced renal cell carcinoma in the
phase 3 CheckMate -025 studyAuthor: B. EscudierAbstract #4509,
Poster Board #132Poster Discussion Session, Genitourinary
(Nonprostate) CancerMonday, June 6, 2016, 4:45 PM – 6:00 PM CDT,
Arie Crown Theater
Bristol-Myers Squibb &
Immuno-Oncology: Advancing Oncology Research
At Bristol-Myers Squibb, we have a vision for the future of
cancer care that is focused on Immuno-Oncology, now considered a
major treatment choice alongside surgery, radiation, chemotherapy
and targeted therapies for certain types of cancer.
We have a comprehensive clinical portfolio of investigational
and approved Immuno-Oncology agents, many of which were discovered
and developed by our scientists. Our ongoing Immuno-Oncology
clinical program is looking at broad patient populations, across
multiple solid tumors and hematologic malignancies, and lines of
therapy and histologies, with the intent of powering our trials for
overall survival and other important measures like durability of
response. We pioneered the research leading to the first regulatory
approval for the combination of two Immuno-Oncology agents, and
continue to study the role of combinations in cancer.
We are also investigating other immune system pathways in the
treatment of cancer including CTLA-4, CD-137, KIR, SLAMF7, PD-1,
GITR, CSF1R, IDO, and LAG-3. These pathways may lead to potential
new treatment options – in combination or monotherapy – to help
patients fight different types of cancers.
Our collaboration with academia, as well as small and large
biotech companies, to research the potential of Immuno-Oncology and
non-Immuno-Oncology combinations, helps achieve our goal of
providing new treatment options in clinical practice.
At Bristol-Myers Squibb, we are committed to changing survival
expectations in hard-to-treat cancers and the way patients live
with cancer.
U.S. FDA APPROVED INDICATIONS FOR
OPDIVO®
OPDIVO® (nivolumab) as a single agent is indicated for the
treatment of patients with BRAF V600 wild-type unresectable or
metastatic melanoma.
OPDIVO® (nivolumab) as a single agent is indicated for the
treatment of patients with 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 confirmatory trials.
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 patients
with classical Hodgkin lymphoma (cHL) that has relapsed or
progressed after autologous hematopoietic stem cell transplantation
(HSCT) and post- transplantation brentuximab vedotin. 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.
Please refer to the end of the Important Safety Information for
a brief description of the patient populations studied in the
Checkmate 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
Immune-mediated pneumonitis, including fatal cases, occurred
with OPDIVO treatment. Across the clinical trial experience with
solid tumors, fatal immune-mediated pneumonitis occurred with
OPDIVO. In addition, in Checkmate 069, there were six patients who
died without resolution of abnormal respiratory findings. Monitor
patients for signs with radiographic imaging and symptoms of
pneumonitis. Administer corticosteroids for Grade 2 or greater
pneumonitis. Permanently discontinue for Grade 3 or 4 and withhold
until resolution for Grade 2. In Checkmate 069 and 067,
immune-mediated pneumonitis occurred in 6% (25/407) of patients
receiving OPDIVO with YERVOY: Fatal (n=1), Grade 3 (n=6), Grade 2
(n=17), and Grade 1 (n=1). In Checkmate 037, 066, and 067,
immune-mediated pneumonitis occurred in 1.8% (14/787) of patients
receiving OPDIVO: Grade 3 (n=2) and Grade 2 (n=12). In Checkmate
057, immune- mediated pneumonitis, including interstitial lung
disease, occurred in 3.4% (10/287) of patients: Grade 3 (n=5),
Grade 2 (n=2), and Grade 1 (n=3). In Checkmate 025, pneumonitis,
including interstitial lung disease, occurred in 5% (21/406) of
patients receiving OPDIVO and 18% (73/397) of patients receiving
everolimus. Immune-mediated pneumonitis occurred in 4.4% (18/406)
of patients receiving OPDIVO: Grade 4 (n=1), Grade 3 (n=4), Grade 2
(n=12), and Grade 1 (n=1). In Checkmate 205 and 039, pneumonitis,
including interstitial lung disease, occurred in 4.9% (13/263) of
patients receiving OPDIVO. Immune-mediated pneumonitis occurred in
3.4% (9/263) of patients receiving OPDIVO: Grade 3 (n=1) and Grade
2 (n=8).
Immune-Mediated Colitis
Immune-mediated colitis can occur with OPDIVO treatment. Monitor
patients for signs and symptoms of colitis. Administer
corticosteroids for Grade 2 (of more than 5 days duration), 3, or 4
colitis. As a single agent, withhold OPDIVO for Grade 2 or 3 and
permanently discontinue for Grade 4 or recurrent colitis upon
restarting OPDIVO. When administered with YERVOY, withhold OPDIVO
for Grade 2 and permanently discontinue for Grade 3 or 4 or
recurrent colitis upon restarting OPDIVO. In Checkmate 069 and 067,
diarrhea or colitis occurred in 56% (228/407) of patients receiving
OPDIVO with YERVOY. Immune-mediated colitis occurred in 26%
(107/407) of patients: Grade 4 (n=2), Grade 3 (n=60), Grade 2
(n=32), and Grade 1 (n=13). In Checkmate 037, 066, and 067,
diarrhea or colitis occurred in 31% (242/787) of patients receiving
OPDIVO. Immune-mediated colitis occurred in 4.1% (32/787) of
patients: Grade 3 (n=20), Grade 2 (n=10), and Grade 1 (n=2). In
Checkmate 057, diarrhea or colitis occurred in 17% (50/287) of
patients receiving OPDIVO. Immune-mediated colitis occurred in 2.4%
(7/287) of patients: Grade 3 (n=3), Grade 2 (n=2), and Grade 1
(n=2). In Checkmate 025, diarrhea or colitis occurred in 25%
(100/406) of patients receiving OPDIVO and 32% (126/397) of
patients receiving everolimus. Immune-mediated diarrhea or colitis
occurred in 3.2% (13/406) of patients receiving OPDIVO: Grade 3
(n=5), Grade 2 (n=7), and Grade 1 (n=1). In Checkmate 205 and 039,
diarrhea or colitis occurred in 30% (80/263) of patients receiving
OPDIVO. Immune-mediated diarrhea (Grade 3) occurred in 1.1% (3/263)
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
Immune-mediated hepatitis can occur with OPDIVO treatment.
Monitor patients for abnormal liver tests prior to and periodically
during treatment. Administer corticosteroids for Grade 2 or greater
transaminase elevations. Withhold for Grade 2 and permanently
discontinue for Grade 3 or 4 immune- mediated hepatitis. In
Checkmate 069 and 067, immune-mediated hepatitis occurred in 13%
(51/407) of patients receiving OPDIVO with YERVOY: Grade 4 (n=8),
Grade 3 (n=37), Grade 2 (n=5), and Grade 1 (n=1). In Checkmate 037,
066, and 067, immune-mediated hepatitis occurred in 2.3% (18/787)
of patients receiving OPDIVO: Grade 4 (n=3), Grade 3 (n=11), and
Grade 2 (n=4). In Checkmate 057, one patient (0.3%) developed
immune-mediated hepatitis. In Checkmate 025, there was an increased
incidence of liver test abnormalities compared to baseline in AST
(33% vs 39%), alkaline phosphatase (32% vs 32%), ALT (22% vs 31%),
and total bilirubin (9% vs 3.5%) in the OPDIVO and everolimus arms,
respectively. Immune-mediated hepatitis requiring systemic
immunosuppression occurred in 1.5% (6/406) of patients receiving
OPDIVO: Grade 3 (n=5) and Grade 2 (n=1). In Checkmate 205 and 039,
hepatitis occurred in 11% (30/263) of patients receiving OPDIVO.
Immune-mediated hepatitis occurred in 3.4% (9/263): Grade 3 (n=7)
and Grade 2 (n=2).
In a separate Phase 3 study of YERVOY 3 mg/kg, severe,
life-threatening, or fatal hepatotoxicity (AST or ALT elevations
>5x the ULN or total bilirubin elevations >3x the ULN; Grade
3-5) occurred in 8 (2%) patients, with fatal hepatic failure in
0.2% and hospitalization in 0.4%.
Immune-Mediated Dermatitis
In a separate Phase 3 study of YERVOY 3 mg/kg, severe,
life-threatening, or fatal immune-mediated dermatitis (eg,
Stevens-Johnson syndrome, toxic epidermal necrolysis, or rash
complicated by full thickness dermal ulceration, or necrotic,
bullous, or hemorrhagic manifestations; Grade 3-5) occurred in 13
(2.5%) patients. 1 (0.2%) patient died as a result of toxic
epidermal necrolysis. 1 additional patient required hospitalization
for severe dermatitis.
Immune-Mediated Neuropathies
In a separate Phase 3 study of YERVOY 3 mg/kg, 1 case of fatal
Guillain-Barré syndrome and 1 case of severe (Grade 3) peripheral
motor neuropathy were reported.
Immune-Mediated Endocrinopathies
Hypophysitis, adrenal insufficiency, thyroid disorders, and type
1 diabetes mellitus can occur with OPDIVO treatment. Monitor
patients for signs and symptoms of hypophysitis, signs and symptoms
of adrenal insufficiency during and after treatment, thyroid
function prior to and periodically during treatment, and
hyperglycemia. Administer corticosteroids for Grade 2 or greater
hypophysitis. Withhold for Grade 2 or 3 and permanently discontinue
for Grade 4 hypophysitis. Administer corticosteroids for Grade 3 or
4 adrenal insufficiency. Withhold for Grade 2 and permanently
discontinue for Grade 3 or 4 adrenal insufficiency. Administer
hormone-replacement therapy for hypothyroidism. Initiate medical
management for control of hyperthyroidism. Administer insulin for
type 1 diabetes. Withhold OPDIVO for Grade 3 and permanently
discontinue for Grade 4 hyperglycemia.
In Checkmate 069 and 067, hypophysitis occurred in 9% (36/407)
of patients receiving OPDIVO with YERVOY: Grade 3 (n=8), Grade 2
(n=25), and Grade 1 (n=3). In Checkmate 037, 066, and 067,
hypophysitis occurred in 0.9% (7/787) of patients receiving OPDIVO:
Grade 3 (n=2), Grade 2 (n=3), and Grade 1 (n=2). In Checkmate 025,
hypophysitis occurred in 0.5% (2/406) of patients receiving OPDIVO:
Grade 3 (n=1) and Grade 1 (n=1). In Checkmate 069 and 067, adrenal
insufficiency occurred in 5% (21/407) of patients receiving OPDIVO
with YERVOY: Grade 4 (n=1), Grade 3 (n=7), Grade 2 (n=11), and
Grade 1 (n=2). In Checkmate 037, 066, and 067, adrenal
insufficiency occurred in 1% (8/787) of patients receiving OPDIVO:
Grade 3 (n=2), Grade 2 (n=5), and Grade 1 (n=1). In Checkmate 057,
0.3% (1/287) of OPDIVO-treated patients developed adrenal
insufficiency. In Checkmate 025, adrenal insufficiency occurred in
2.0% (8/406) of patients receiving OPDIVO: Grade 3 (n=3), Grade 2
(n=4), and Grade 1 (n=1). In Checkmate 205 and 039, adrenal
insufficiency (Grade 2) occurred in 0.4% (1/263) of patients
receiving OPDIVO. In Checkmate 069 and 067, hypothyroidism or
thyroiditis occurred in 22% (89/407) of patients receiving OPDIVO
with YERVOY: Grade 3 (n=6), Grade 2 (n=47), and Grade 1 (n=36).
Hyperthyroidism occurred in 8% (34/407) of patients: Grade 3 (n=4),
Grade 2 (n=17), and Grade 1 (n=13). In Checkmate 037, 066, and 067,
hypothyroidism or thyroiditis occurred in 9% (73/787) of patients
receiving OPDIVO: Grade 3 (n=1), Grade 2 (n=37), Grade 1 (n=35).
Hyperthyroidism occurred in 4.4% (35/787) of patients receiving
OPDIVO: Grade 3 (n=1), Grade 2 (n=12), and Grade 1 (n=22). In
Checkmate 057, Grade 1 or 2 hypothyroidism, including thyroiditis,
occurred in 7% (20/287) and elevated thyroid stimulating hormone
occurred in 17% of patients receiving OPDIVO. Grade 1 or 2
hyperthyroidism occurred in 1.4% (4/287) of patients. In Checkmate
025, thyroid disease occurred in 11% (43/406) of patients receiving
OPDIVO, including one Grade 3 event, and in 3.0% (12/397) of
patients receiving everolimus. Hypothyroidism/thyroiditis occurred
in 8% (33/406) of patients receiving OPDIVO: Grade 3 (n=2), Grade 2
(n=17), and Grade 1 (n=14). Hyperthyroidism occurred in 2.5%
(10/406) of patients receiving OPDIVO: Grade 2 (n=5) and Grade 1
(n=5). In Checkmate 205 and 039, hypothyroidism/thyroiditis
occurred in 12% (32/263) of patients receiving OPDIVO: Grade 2
(n=18) and Grade 1: (n=14). Hyperthyroidism occurred in 1.5%
(4/263) of patients receiving OPDIVO: Grade 2: (n=3) and Grade 1
(n=1). In Checkmate 069 and 067, diabetes mellitus or diabetic
ketoacidosis occurred in 1.5% (6/407) of patients: Grade 4 (n=3),
Grade 3 (n=1), Grade 2 (n=1), and Grade 1 (n=1). In Checkmate 037,
066, and 067, diabetes mellitus or diabetic ketoacidosis occurred
in 0.8% (6/787) of patients receiving OPDIVO: Grade 3 (n=2), Grade
2 (n=3), and Grade 1 (n=1). In Checkmate 025, hyperglycemic adverse
events occurred in 9% (37/406) patients.
Diabetes mellitus or diabetic ketoacidosis occurred in 1.5%
(6/406) of patients receiving OPDIVO: Grade 3 (n=3), Grade 2 (n=2),
and Grade 1 (n=1). In Checkmate 205 and 039, diabetes mellitus
occurred in 0.8% (2/263) of patients receiving OPDIVO: Grade 3
(n=1) and Grade 1 (n=1).
In a separate Phase 3 study of YERVOY 3 mg/kg, severe to
life-threatening immune-mediated endocrinopathies (requiring
hospitalization, urgent medical intervention, or interfering with
activities of daily living; Grade 3-4) occurred in 9 (1.8%)
patients. All 9 patients had hypopituitarism, and some had
additional concomitant endocrinopathies such as adrenal
insufficiency, hypogonadism, and hypothyroidism. 6 of the 9
patients were hospitalized for severe endocrinopathies.
Immune-Mediated Nephritis and Renal Dysfunction
Immune-mediated nephritis can occur with OPDIVO treatment.
Monitor patients for elevated serum creatinine prior to and
periodically during treatment. For Grade 2 or 3 increased serum
creatinine, withhold and administer corticosteroids; if worsening
or no improvement occurs, permanently discontinue. Administer
corticosteroids for Grade 4 serum creatinine elevation and
permanently discontinue. In Checkmate 069 and 067, immune-mediated
nephritis and renal dysfunction occurred in 2.2% (9/407) of
patients: Grade 4 (n=4), Grade 3 (n=3), and Grade 2 (n=2). In
Checkmate 037, 066, and 067, nephritis and renal dysfunction of any
grade occurred in 5% (40/787) of patients receiving OPDIVO.
Immune-mediated nephritis and renal dysfunction occurred in 0.8%
(6/787) of patients: Grade 3 (n=4) and Grade 2 (n=2). In Checkmate
057, Grade 2 immune-mediated renal dysfunction occurred in 0.3%
(1/287) of patients receiving OPDIVO. In Checkmate 025, renal
injury occurred in 7% (27/406) of patients receiving OPDIVO and
3.0% (12/397) of patients receiving everolimus. Immune-mediated
nephritis and renal dysfunction occurred in 3.2% (13/406) of
patients receiving OPDIVO: Grade 5 (n=1), Grade 4 (n=1), Grade 3
(n=5), and Grade 2 (n=6). In Checkmate 205 and 039, nephritis and
renal dysfunction occurred in 4.9% (13/263) of patients treated
with OPDIVO. This included one reported case (0.3%) of Grade 3
autoimmune nephritis.
Immune-Mediated Rash
Immune-mediated rash can occur with OPDIVO treatment. Severe
rash (including rare cases of fatal toxic epidermal necrolysis)
occurred in the clinical program of OPDIVO. Monitor patients for
rash. Administer corticosteroids for Grade 3 or 4 rash. Withhold
for Grade 3 and permanently discontinue for Grade 4. In Checkmate
069 and 067, immune-mediated rash occurred in 22.6% (92/407) of
patients receiving OPDIVO with YERVOY: Grade 3 (n=15), Grade 2
(n=31), and Grade 1 (n=46). In Checkmate 037, 066, and 067,
immune-mediated rash occurred in 9% (72/787) of patients receiving
OPDIVO: Grade 3 (n=7), Grade 2 (n=15), and Grade 1 (n=50). In
Checkmate 057, immune-mediated rash occurred in 6% (17/287) of
patients receiving OPDIVO including four Grade 3 cases. In
Checkmate 025, rash occurred in 28% (112/406) of patients receiving
OPDIVO and 36% (143/397) of patients receiving everolimus. Immune-
mediated rash, defined as a rash treated with systemic or topical
corticosteroids, occurred in 7% (30/406) of patients receiving
OPDIVO: Grade 3 (n=4), Grade 2 (n=7), and Grade 1 (n=19). In
Checkmate 205 and 039, rash occurred in 22% (58/263) of patients
receiving OPDIVO. Immune-mediated rash occurred in 7% (18/263) of
patients on OPDIVO: Grade 3 (n=4), Grade 2 (n=3), and Grade 1
(n=11).
Immune-Mediated Encephalitis
Immune-mediated encephalitis can occur with OPDIVO treatment.
Withhold OPDIVO in patients with new-onset moderate to severe
neurologic signs or symptoms and evaluate to rule out other causes.
If other etiologies are ruled out, administer corticosteroids and
permanently discontinue OPDIVO for immune-mediated encephalitis. In
Checkmate 067, encephalitis was identified in one patient (0.2%)
receiving OPDIVO with YERVOY. In Checkmate 057, fatal limbic
encephalitis occurred in one patient (0.3%) receiving OPDIVO. In
Checkmate 205 and 039, encephalitis occurred in 0.8% (2/263) of
patients after allogeneic HSCT after OPDIVO.
Other Immune-Mediated Adverse Reactions
Based on the severity of adverse reaction, permanently
discontinue or withhold treatment, administer high-dose
corticosteroids, and, if appropriate, initiate hormone-replacement
therapy. In < 1.0% of patients receiving OPDIVO, the following
clinically significant, immune-mediated adverse reactions occurred:
uveitis, iritis, pancreatitis, facial and abducens nerve paresis,
demyelination, polymyalgia rheumatica, autoimmune neuropathy,
Guillain-Barré syndrome, hypopituitarism, systemic inflammatory
response syndrome, gastritis, duodenitis, and sarcoidosis. Across
clinical trials of OPDIVO as a single agent administered at doses
of 3 mg/kg and 10 mg/kg, additional clinically significant, immune-
mediated adverse reactions were identified: motor dysfunction,
vasculitis, and myasthenic syndrome.
Infusion Reactions
Severe infusion reactions have been reported in <1.0% of
patients in clinical trials of OPDIVO. Discontinue OPDIVO in
patients with Grade 3 or 4 infusion reactions. Interrupt or slow
the rate of infusion in patients with Grade 1 or 2. In Checkmate
069 and 067, infusion- related reactions occurred in 2.5% (10/407)
of patients receiving OPDIVO with YERVOY: Grade 2 (n=6) and Grade 1
(n=4). In Checkmate 037, 066, and 067, Grade 2 infusion related
reactions occurred in 2.7% (21/787) of patients receiving OPDIVO:
Grade 3 (n=2), Grade 2 (n=8), and Grade 1 (n=11). In Checkmate 057,
Grade 2 infusion reactions requiring corticosteroids occurred in
1.0% (3/287) of patients receiving OPDIVO. In Checkmate 025,
hypersensitivity/infusion-related reactions occurred in 6% (25/406)
of patients receiving OPDIVO and 1.0% (4/397) of patients receiving
everolimus. In Checkmate 205 and 039, hypersensitivity/infusion-
related reactions occurred in 16% (42/263) of patients receiving
OPDIVO: Grade 3 (n=2), Grade 2 (n=24), and Grade 1 (n=16).
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 SCT 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 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 relative to the OPDIVO arm. 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 037,
serious adverse reactions occurred in 41% of patients receiving
OPDIVO. Grade 3 and 4 adverse reactions occurred in 42% of patients
receiving OPDIVO. The most frequent Grade 3 and 4 adverse drug
reactions reported in 2% to <5% of patients receiving OPDIVO
were abdominal pain, hyponatremia, increased aspartate
aminotransferase, and increased lipase. In Checkmate 066, serious
adverse reactions occurred in 36% of patients receiving OPDIVO.
Grade 3 and 4 adverse reactions occurred in 41% of patients
receiving OPDIVO. The most frequent Grade 3 and 4 adverse reactions
reported in ≥2% of patients receiving OPDIVO were
gamma-glutamyltransferase increase (3.9%) and diarrhea (3.4%). In
Checkmate 057, serious adverse reactions occurred in 47% of
patients receiving OPDIVO. The most frequent serious adverse
reactions reported in ≥2% of patients were pneumonia, pulmonary
embolism, dyspnea, pleural effusion, and respiratory failure. In
Checkmate 025, serious adverse reactions occurred in 47% of
patients receiving OPDIVO. The most frequent serious adverse
reactions reported in ≥2% of patients were acute kidney injury,
pleural effusion, pneumonia, diarrhea, and hypercalcemia. In
Checkmate 205 and 039, among all patients (safety population
[n=263]), adverse reactions leading to discontinuation (4.2%) or to
dosing delays (23%) occurred. The most frequent serious adverse
reactions reported in 1% of patients were infusion-related
reaction, pneumonia, pleural effusion, pyrexia, rash and
pneumonitis. Ten patients died from causes other than disease
progression, including 6 who died from complications of allogeneic
HSCT. Serious adverse reactions occurred in 21% of patients in the
safety population (n=263) and 27% of patients in the subset of
patients evaluated for efficacy (efficacy population [n=95]).
Common Adverse Reactions
In Checkmate 067, the most common (≥20%) adverse reactions in
the OPDIVO plus YERVOY arm 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 arm
were fatigue (53%), rash (40%), diarrhea (31%), and nausea (28%).
In Checkmate 037, the most common adverse reaction (≥20%) reported
with OPDIVO was rash (21%). In Checkmate 066, the most common
adverse reactions (≥20%) reported with OPDIVO vs dacarbazine were
fatigue (49% vs 39%), musculoskeletal pain (32% vs 25%), rash (28%
vs 12%), and pruritus (23% vs 12%). In Checkmate 057, the most
common adverse reactions (≥20%) reported with OPDIVO were fatigue
(49%), musculoskeletal pain (36%), cough (30%), decreased appetite
(29%), and constipation (23%). In Checkmate 025, the most common
adverse reactions (≥20%) reported in patients receiving OPDIVO vs
everolimus were asthenic conditions (56% vs 57%), cough (34% vs
38%), nausea (28% vs 29%), rash (28% vs 36%), dyspnea (27% vs 31%),
diarrhea (25% vs 32%), constipation (23% vs 18%), decreased
appetite (23% vs 30%), back pain (21% vs 16%), and arthralgia (20%
vs 14%). In Checkmate 205 and 039, among all patients (safety
population [n=263]) and the subset of patients in the efficacy
population (n=95), respectively, the most common adverse reactions
(reported in at least 20%) were fatigue (32% and 43%), upper
respiratory tract infection (28% and 48%), pyrexia (24% and 35%),
diarrhea (23% and 30%), and cough (22% and 35%). In the subset of
patients in the efficacy population (n=95), the most common adverse
reactions also included rash (31%), musculoskeletal pain (27%),
pruritus (25%), nausea (23%), arthralgia (21%), and peripheral
neuropathy (21%).
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 069 and 067 - advanced melanoma alone or in
combination with YERVOY; Checkmate 037 and 066 - advanced
melanoma; Checkmate 057 – non-squamous non-small cell lung
cancer (NSCLC); Checkmate 025 - renal cell carcinoma;
Checkmate 205/039 - classical Hodgkin lymphoma
U.S. FDA APPROVED INDICATIONS FOR
YERVOY®
YERVOY® (ipilimumab) is indicated for the treatment of
unresectable or metastatic melanoma.
YERVOY® (ipilimumab) is indicated for the adjuvant treatment of
patients with cutaneous melanoma with pathologic involvement of
regional lymph nodes of more than 1 mm who have undergone complete
resection, including total lymphadenectomy.
IMPORTANT SAFETY INFORMATION
WARNING: IMMUNE-MEDIATED ADVERSE REACTIONS
YERVOY (ipilimumab) 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.
Permanently discontinue YERVOY and initiate systemic
high-dose corticosteroid therapy for severe immune-mediated
reactions.
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.
Recommended Dose Modifications
Endocrine: Withhold YERVOY for systemic endocrinopathy. Resume
YERVOY in patients with complete or partial resolution of adverse
reactions (Grade 0-1) and who are receiving <7.5 mg prednisone
or equivalent per day. Permanently discontinue YERVOY for
symptomatic reactions lasting 6 weeks or longer or an inability to
reduce corticosteroid dose to 7.5 mg prednisone or equivalent per
day.
Ophthalmologic: Permanently discontinue YERVOY for Grade 2-4
reactions not improving to Grade 1 within 2 weeks while receiving
topical therapy or requiring systemic treatment.
All Other Organ Systems: Withhold YERVOY for Grade 2 adverse
reactions. Resume YERVOY in patients with complete or partial
resolution of adverse reactions (Grade 0-1) and who are receiving
<7.5 mg prednisone or equivalent per day. Permanently
discontinue YERVOY for Grade 2 reactions lasting 6 weeks or longer,
an inability to reduce corticosteroid dose to 7.5 mg prednisone or
equivalent per day, and Grade 3 or 4 adverse reactions.
Immune-mediated Enterocolitis
Immune-mediated enterocolitis, including fatal cases, can occur
with YERVOY. Monitor patients for signs and symptoms of
enterocolitis (such as diarrhea, abdominal pain, mucus or blood in
stool, with or without fever) and of bowel perforation (such as
peritoneal signs and ileus). In symptomatic patients, rule out
infectious etiologies and consider endoscopic evaluation for
persistent or severe symptoms. Withhold YERVOY for moderate
enterocolitis; administer anti-diarrheal treatment and, if
persistent for >1 week, initiate systemic corticosteroids (0.5
mg/kg/day prednisone or equivalent). Permanently discontinue YERVOY
in patients with severe enterocolitis and initiate systemic
corticosteroids (1-2 mg/kg/day of prednisone or equivalent). Upon
improvement to ≤Grade 1, initiate corticosteroid taper and continue
over at least 1 month. In clinical trials, rapid corticosteroid
tapering resulted in recurrence or worsening symptoms of
enterocolitis in some patients. Consider adding anti-TNF or other
immunosuppressant agents for management of immune-mediated
enterocolitis unresponsive to systemic corticosteroids within 3-5
days or recurring after symptom improvement. In patients receiving
YERVOY 3 mg/kg in Trial 1, severe, life-threatening, or fatal
(diarrhea of ≥7 stools above baseline, fever, ileus, peritoneal
signs; Grade 3-5) immune-mediated enterocolitis occurred in 34
YERVOY-treated patients (7%) and moderate (diarrhea with up to 6
stools above baseline, abdominal pain, mucus or blood in
stool; Grade 2) enterocolitis occurred in 28
YERVOY-treated patients (5%). Across all YERVOY-treated patients
(n=511), 5 (1%) developed intestinal perforation, 4 (0.8%) died as
a result of complications, and 26 (5%) were hospitalized for severe
enterocolitis. Infliximab was administered to 5 (8%) of the 62
patients with moderate, severe, or life-threatening immune-mediated
enterocolitis following inadequate response to corticosteroids. In
patients receiving YERVOY 10 mg/kg in Trial 2, Grade 3-5
immune-mediated enterocolitis occurred in 76 patients (16%) and
Grade 2 enterocolitis occurred in 68 patients (14%). Seven (1.5%)
developed intestinal perforation and 3 patients (0.6%) died as a
result of complications.
Immune-mediated Hepatitis
Immune-mediated hepatitis, including fatal cases, can occur with
YERVOY. Monitor LFTs (hepatic transaminase and bilirubin levels)
and assess patients for signs and symptoms of hepatotoxicity before
each dose of YERVOY. In patients with hepatotoxicity, rule out
infectious or malignant causes and increase frequency of LFT
monitoring until resolution. Withhold YERVOY in patients with Grade
2 hepatotoxicity. Permanently discontinue YERVOY in patients with
Grade 3-4 hepatotoxicity and administer systemic
corticosteroids (1-2 mg/kg/day of prednisone or
equivalent). When LFTs show sustained improvement or return to
baseline, initiate corticosteroid tapering and continue over 1
month. Across the clinical development program for YERVOY,
mycophenolate treatment has been administered in patients with
persistent severe hepatitis despite high-dose corticosteroids. In
patients receiving YERVOY 3 mg/kg in Trial 1, severe,
life-threatening, or fatal hepatotoxicity (AST or ALT elevations
>5× the ULN or total bilirubin elevations >3× the ULN; Grade
3-5) occurred in 8 YERVOY-treated patients (2%), with fatal hepatic
failure in 0.2% and hospitalization in 0.4%. An additional 13
patients (2.5%) experienced moderate hepatotoxicity manifested by
LFT abnormalities (AST or ALT elevations >2.5× but ≤5× the ULN
or total bilirubin elevation >1.5× but ≤3× the ULN; Grade 2). In
a dose-finding trial, Grade 3 increases in transaminases with or
without concomitant increases in total bilirubin occurred in 6 of
10 patients who received concurrent YERVOY (3 mg/kg) and
vemurafenib (960 mg BID or 720 mg BID). In patients receiving
YERVOY 10 mg/kg in Trial 2, Grade 3-4 immune-mediated hepatitis
occurred in 51 patients (11%) and moderate Grade 2 immune-mediated
hepatitis occurred in 22 patients (5%). Liver biopsy performed in 6
patients with Grade 3-4 hepatitis showed evidence of toxic or
autoimmune hepatitis.
Immune-mediated Dermatitis
Immune-mediated dermatitis, including fatal cases, can occur
with YERVOY. Monitor patients for signs and symptoms of dermatitis
such as rash and pruritus. Unless an alternate etiology has been
identified, signs or symptoms of dermatitis should be considered
immune-mediated. Treat mild to moderate dermatitis (e.g., localized
rash and pruritus) symptomatically; administer topical or systemic
corticosteroids if there is no improvement within 1 week. Withhold
YERVOY in patients with moderate to severe signs and symptoms.
Permanently discontinue YERVOY in patients with severe,
life-threatening, or fatal immune-mediated dermatitis (Grade 3-5).
Administer systemic corticosteroids (1-2 mg/kg/day of
prednisone or equivalent). When dermatitis is controlled,
corticosteroid tapering should occur over a period of at least 1
month. In patients receiving YERVOY 3 mg/kg in Trial 1, severe,
life-threatening, or fatal immune-mediated dermatitis (e.g.,
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
YERVOY-treated patients (2.5%); 1 patient (0.2%) died as a result
of toxic epidermal necrolysis and 1 additional patient required
hospitalization for severe dermatitis. There were 63 patients (12%)
with moderate (Grade 2) dermatitis. In patients receiving YERVOY 10
mg/kg in Trial 2, Grade 3-4 immune-mediated dermatitis occurred in
19 patients (4%). There were 99 patients (21%) with moderate Grade
2 dermatitis.
Immune-mediated Neuropathies
Immune-mediated neuropathies, including fatal cases, can occur
with YERVOY. Monitor for symptoms of motor or sensory neuropathy
such as unilateral or bilateral weakness, sensory alterations, or
paresthesia. Withhold YERVOY in patients with moderate neuropathy
(not interfering with daily activities). Permanently discontinue
YERVOY in patients with severe neuropathy (interfering with daily
activities), such as Guillain-Barre-like syndromes. Institute
medical intervention as appropriate for management for severe
neuropathy. Consider initiation of systemic corticosteroids (1-2
mg/kg/day of prednisone or equivalent) for severe neuropathies. In
patients receiving YERVOY 3 mg/kg in Trial 1, 1 case of fatal
Guillain-Barré syndrome and 1 case of severe (Grade 3) peripheral
motor neuropathy were reported. Across the clinical development
program of YERVOY, myasthenia gravis and additional cases of
Guillain-Barré syndrome have been reported. In patients receiving
YERVOY 10 mg/kg in Trial 2, Grade 3-5 immune-mediated neuropathy
occurred in 8 patients (2%); the sole fatality was due to
complications of Guillain-Barré syndrome. Moderate Grade 2
immune-mediated neuropathy occurred in 1 patient (0.2%).
Immune-mediated Endocrinopathies
Immune-mediated endocrinopathies, including life-threatening
cases, can occur with YERVOY. Monitor patients for clinical signs
and symptoms of hypophysitis, adrenal insufficiency (including
adrenal crisis), and hyper- or hypothyroidism. Patients may present
with fatigue, headache, mental status changes, abdominal pain,
unusual bowel habits, and hypotension, or nonspecific symptoms
which may resemble other causes such as brain metastasis or
underlying disease. Unless an alternate etiology has been
identified, signs or symptoms should be considered immune-mediated.
Monitor clinical chemistries, adrenocorticotropic hormone (ACTH)
level, and thyroid function tests at the start of treatment, before
each dose, and as clinically indicated based on symptoms. In a
limited number of patients, hypophysitis was diagnosed by imaging
studies through enlargement of the pituitary gland. Withhold YERVOY
in symptomatic patients and consider referral to an
endocrinologist. Initiate systemic corticosteroids (1-2 mg/kg/day
of prednisone or equivalent) and initiate appropriate hormone
replacement therapy. In patients receiving YERVOY 3 mg/kg in Trial
1, 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 YERVOY-treated patients (1.8%). 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. Moderate endocrinopathy (requiring hormone
replacement or medical intervention; Grade 2) occurred in 12
patients (2.3%) and consisted of hypothyroidism, adrenal
insufficiency, hypopituitarism, and 1 case each of hyperthyroidism
and Cushing's syndrome. The median time to onset of moderate to
severe immune-mediated endocrinopathy was 2.5 months and ranged up
to 4.4 months after the initiation of YERVOY. In patients receiving
YERVOY 10 mg/kg in Trial 2, Grade 3-4 immune-mediated
endocrinopathies occurred in 39 patients (8%) and Grade 2
immune-mediated endocrinopathies occurred in 93 patients (20%). Of
the 39 patients with Grade 3-4 immune-mediated endocrinopathies, 35
patients had hypopituitarism (associated with 1 or more secondary
endocrinopathies, e.g., adrenal insufficiency, hypogonadism, and
hypothyroidism), 3 patients had hyperthyroidism, and 1 had primary
hypothyroidism. The median time to onset of Grade 3-4
immune-mediated endocrinopathy was 2.2 months (range: 2 days-8
months). Twenty-seven (69.2%) of the 39 patients were hospitalized
for immune-mediated endocrinopathies. Of the 93 patients with Grade
2 immune-mediated endocrinopathy, 74 had primary hypopituitarism
(associated with 1 or more secondary endocrinopathy, e.g., adrenal
insufficiency, hypogonadism, and hypothyroidism), 9 had primary
hypothyroidism, 3 had hyperthyroidism, 3 had thyroiditis with hypo-
or hyperthyroidism, 2 had hypogonadism, 1 had both hyperthyroidism
and hypopituitarism, and 1 subject developed Graves’
ophthalmopathy. The median time to onset of Grade 2 immune-mediated
endocrinopathy was 2.1 months (range: 9 days-19.3 months).
Other Immune-mediated Adverse Reactions, Including Ocular
Manifestations
Permanently discontinue YERVOY for clinically significant or
severe immune-mediated adverse reactions. Initiate systemic
corticosteroids (1-2 mg/kg/day of prednisone or equivalent) for
severe immune-mediated adverse reactions. Administer corticosteroid
eye drops for uveitis, iritis, or episcleritis. Permanently
discontinue YERVOY for immune-mediated ocular disease unresponsive
to local immunosuppressive therapy. In Trial 1, the following
clinically significant immune-mediated adverse reactions were seen
in <1% of YERVOY-treated patients: nephritis, pneumonitis,
meningitis, pericarditis, uveitis, iritis, and hemolytic anemia. In
Trial 2, the following clinically significant immune-mediated
adverse reactions were seen in <1% of YERVOY-treated patients
unless specified: eosinophilia (2.1%), pancreatitis (1.3%),
meningitis, pneumonitis, sarcoidosis, pericarditis, uveitis and
fatal myocarditis. Across 21 dose-ranging trials administering
YERVOY at doses of 0.1 to 20 mg/kg (n=2478), the following likely
immune-mediated adverse reactions were also reported with <1%
incidence: angiopathy, temporal arteritis, vasculitis, polymyalgia
rheumatica, conjunctivitis, blepharitis, episcleritis, scleritis,
iritis, leukocytoclastic vasculitis, erythema multiforme,
psoriasis, arthritis, autoimmune thyroiditis, neurosensory
hypoacusis, autoimmune central neuropathy (encephalitis), myositis,
polymyositis, ocular myositis, hemolytic anemia, and nephritis.
Embryo-fetal Toxicity
Based on its mechanism of action, YERVOY can cause fetal harm
when administered to a pregnant woman. The effects of YERVOY are
likely to be greater during the second and third trimesters of
pregnancy. Advise pregnant women of the potential risk to a fetus.
Advise females of reproductive potential to use effective
contraception during treatment with a YERVOY-containing regimen and
for 3 months after the last dose of YERVOY.
Lactation
It is not known whether YERVOY is secreted in human milk. Advise
women to discontinue nursing during treatment with YERVOY and for 3
months following the final dose.
Common Adverse Reactions
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%). The most common adverse
reactions (≥5%) in patients who received YERVOY at 10 mg/kg were
rash (50%), diarrhea (49%), fatigue (46%), pruritus (45%), headache
(33%), weight loss (32%), nausea (25%), pyrexia (18%), colitis
(16%), decreased appetite (14%), vomiting (13%), and insomnia
(10%).
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%).
SPRYCEL® (dasatinib) U.S. INDICATIONS &
IMPORTANT SAFETY INFORMATION
INDICATIONS
SPRYCEL® (dasatinib) is indicated for the treatment of adults
with:
- Newly diagnosed adults with
Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia
(CML) in chronic phase.
- Adults with chronic, accelerated, or
myeloid or lymphoid blast phase Ph+ CML with resistance or
intolerance to prior therapy including imatinib.
- Adults with Philadelphia
chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) with
resistance or intolerance to prior therapy.
IMPORTANT SAFETY INFORMATION
Myelosuppression:
Treatment with SPRYCEL is associated with severe (NCI CTC Grade
3/4) thrombocytopenia, neutropenia, and anemia, which occur earlier
and more frequently in patients with advanced phase CML or Ph+ ALL
than in patients with chronic phase CML.
- In patients with chronic phase CML,
perform complete blood counts (CBCs) every 2 weeks for 12 weeks,
then every 3 months thereafter, or as clinically indicated.
- In patients with advanced phase CML or
Ph+ ALL, perform CBCs weekly for the first 2 months and then
monthly thereafter, or as clinically indicated.
- Myelosuppression is generally
reversible and usually managed by withholding SPRYCEL temporarily
and/or dose reduction.
- In clinical studies, myelosuppression
may have also been managed by discontinuation of study
therapy.
- Hematopoietic growth factor has been
used in patients with resistant myelosuppression.
Bleeding Related Events:
SPRYCEL caused thrombocytopenia in human subjects. In addition,
dasatinib caused platelet dysfunction in vitro. In all CML or Ph+
ALL clinical studies, ≥grade 3 central nervous system (CNS)
hemorrhages, including fatalities, occurred in <1% of patients
receiving SPRYCEL. Grade 3 or greater gastrointestinal hemorrhage,
including fatalities, occurred in 4% of patients and generally
required treatment interruptions and transfusions. Other cases of
≥grade 3 hemorrhage occurred in 2% of patients.
- Most bleeding events in clinical
studies were associated with severe thrombocytopenia.
- Concomitant medications that inhibit
platelet function or anticoagulants may increase the risk of
hemorrhage.
Fluid Retention:
SPRYCEL may cause fluid retention. After 5 years of follow-up in
the randomized newly diagnosed chronic phase CML study (n=258),
grade 3/4 fluid retention was reported in 5% of patients, including
3% of patients with grade 3/4 pleural effusion. In patients with
newly diagnosed or imatinib resistant or intolerant chronic phase
CML, grade 3/4 fluid retention occurred in 6% of patients treated
with SPRYCEL at the recommended dose (n=548). In patients with
advanced phase CML or Ph+ ALL treated with SPRYCEL at the
recommended dose (n=304), grade 3/4 fluid retention was reported in
8% of patients, including grade 3/4 pleural effusion reported in 7%
of patients.
- Patients who develop symptoms of
pleural effusion or other fluid retention, such as new or worsened
dyspnea on exertion or at rest, pleuritic chest pain, or dry cough
should be evaluated promptly with a chest x-ray or additional
diagnostic imaging as appropriate.
- Fluid retention events were typically
managed by supportive care measures that may include diuretics or
short courses of steroids.
- Severe pleural effusion may require
thoracentesis and oxygen therapy.
- Consider dose reduction or treatment
interruption.
Cardiovascular Events:
After 5 years of follow-up in the randomized newly diagnosed
chronic phase CML trial (n=258), the following cardiac adverse
events occurred:
- Cardiac ischemic events (3.9% dasatinib
vs 1.6% imatinib), cardiac related fluid retention (8.5% dasatinib
vs 3.9% imatinib), and conduction system abnormalities, most
commonly arrhythmia and palpitations (7.0% dasatinib vs 5.0%
imatinib). Two cases (0.8%) of peripheral arterial occlusive
disease occurred with imatinib and 2 (0.8%) transient ischemic
attacks occurred with dasatinib.
Monitor patients for signs or symptoms consistent with cardiac
dysfunction and treat appropriately.
Pulmonary Arterial Hypertension (PAH):
SPRYCEL may increase the risk of developing PAH, which may occur
any time after initiation, including after more than 1 year of
treatment. Manifestations include dyspnea, fatigue, hypoxia, and
fluid retention. PAH may be reversible on discontinuation of
SPRYCEL.
- Evaluate patients for signs and
symptoms of underlying cardiopulmonary disease prior to initiating
SPRYCEL and during treatment. If PAH is confirmed, SPRYCEL should
be permanently discontinued.
QT Prolongation:
In vitro data suggest that SPRYCEL has the potential to prolong
cardiac ventricular repolarization (QT interval).
- Most bleeding events in clinical
studies were associated with severe thrombocytopenia.
- Concomitant medications that inhibit
platelet function or anticoagulants may increase the risk of
hemorrhage.
Severe Dermatologic Reactions:
Cases of severe mucocutaneous dermatologic reactions, including
Stevens-Johnson syndrome and erythema multiforme, have been
reported in patients treated with SPRYCEL.
- Discontinue permanently in patients who
experience a severe mucocutaneous reaction during treatment if no
other etiology can be identified.
Tumor Lysis Syndrome (TLS):
TLS has been reported in patients with resistance to prior
imatinib therapy, primarily in advanced phase disease.
- Due to potential for TLS, maintain
adequate hydration, correct uric acid levels prior to initiating
therapy with SPRYCEL, and monitor electrolyte levels.
- Patients with advanced stage disease
and/or high tumor burden may be at increased risk and should be
monitored more frequently.
Embryo-Fetal Toxicity:
Based on limited human data, SPRYCEL can cause fetal harm when
administered to a pregnant woman. Hydrops fetalis, fetal leukopenia
and fetal thrombocytopenia have been reported with maternal
exposure to SPRYCEL. Transplacental transfer of dasatinib has been
measured in fetal plasma and amniotic fluid at concentrations
comparable to those in maternal plasma.
- Advise females of reproductive
potential to avoid pregnancy, which may include the use of
effective contraception, during treatment with SPRYCEL and for 30
days after the final dose.
Lactation:
No data are available regarding the presence of dasatinib in
human milk, the effects of the drug on the breastfed infant or the
effects of the drug on milk production. However, dasatinib is
present in the milk of lactating rats.
- Because of the potential for serious
adverse reactions in nursing infants from SPRYCEL, breastfeeding is
not recommended during treatment with SPRYCEL and for 2 weeks after
the final dose.
Drug Interactions:
SPRYCEL is a CYP3A4 substrate and a weak time-dependent
inhibitor of CYP3A4.
- Drugs that may increase SPRYCEL plasma
concentrations are:
- CYP3A4 inhibitors: Concomitant
use of SPRYCEL and drugs that inhibit CYP3A4 should be avoided. If
administration of a potent CYP3A4 inhibitor cannot be avoided,
close monitoring for toxicity and a SPRYCEL dose reduction should
be considered
- Strong CYP3A4 inhibitors (eg,
ketoconazole, itraconazole, clarithromycin, atazanavir, indinavir,
nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin,
voriconazole). If SPRYCEL must be administered with a strong CYP3A4
inhibitor, a dose decrease or temporary discontinuation should be
considered
- Grapefruit juice may also
increase plasma concentrations of SPRYCEL and should be
avoided
- Drugs that may decrease SPRYCEL plasma
concentrations are:
- CYP3A4 inducers: If SPRYCEL must
be administered with a CYP3A4 inducer, a dose increase in SPRYCEL
should be considered
- Strong CYP3A4 inducers (eg,
dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin,
phenobarbital) should be avoided. Alternative agents with less
enzyme induction potential should be considered. If the dose of
SPRYCEL is increased, the patient should be monitored carefully for
toxicity
- St John’s Wort may decrease
SPRYCEL plasma concentrations unpredictably and should be
avoided
- Antacids may decrease SPRYCEL
drug levels. Simultaneous administration of SPRYCEL and antacids
should be avoided. If antacid therapy is needed, the antacid dose
should be administered at least 2 hours prior to or 2 hours after
the dose of SPRYCEL
- H2 antagonists/proton
pump inhibitors (eg, famotidine and omeprazole): Long-term
suppression of gastric acid secretion by use of H2 antagonists or
proton pump inhibitors is likely to reduce SPRYCEL exposure.
Therefore, concomitant use of H2 antagonists or proton pump
inhibitors with SPRYCEL is not recommended
- Drugs that may have their plasma
concentration altered by SPRYCEL are:
- CYP3A4 substrates (eg,
simvastatin) with a narrow therapeutic index should be administered
with caution in patients receiving SPRYCEL
Adverse Reactions:
- In newly diagnosed chronic phase CML
patients:
- Drug-related serious adverse events
(SAEs) were reported for 16.7% of SPRYCEL-treated patients. Serious
adverse reactions reported in ≥5% of patients included pleural
effusion (5%).
- Most common adverse reactions (≥15%)
included myelosuppression, fluid retention, and diarrhea.
- In patients resistant or intolerant to
prior imatinib therapy:
- Drug-related SAEs were reported for
26.1% of Sprycel-treated patients treated at the recommended dose
of 100 mg once daily in the randomized dose-optimization trial of
patients with chronic phase CML resistant or intolerant to prior
imatinib therapy. Serious adverse reactions reported in ≥5% of
patients included pleural effusion (10%).
- Most common adverse reactions (≥15%)
included myelosuppression, fluid retention events, diarrhea,
headache, fatigue, dyspnea, skin rash, nausea, hemorrhage and
musculoskeletal pain.
Please see the full Prescribing Information
here.
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 the Bristol-Myers Squibb and
AbbVie Collaboration
Bristol-Myers Squibb and AbbVie are co-developing Empliciti,
with Bristol-Myers Squibb solely responsible for commercial
activities.
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 as a single agent or in combination with Yervoy, or
Empliciti will receive regulatory approval for the additional
indications described herein. 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, 2015 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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version on businesswire.com: http://www.businesswire.com/news/home/20160518005444/en/
Bristol-Myers Squibb CompanyMedia:Audrey
Abernathy, 609-419-5375Cell:
919-605-4521audrey.abernathy@bms.comorInvestors:Ranya Dajani,
609-252-5330ranya.dajani@bms.comorBill Szablewski,
609-252-5894william.szablewski@bms.com
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