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
PRINCETON, N.J.--(BUSINESS WIRE)--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.
24
th
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: Yau
Abstract: #4012
Poster
Discussion Session: Gastrointestinal (Noncolorectal) Cancer
Monday,
June 3, Poster Display: 8-11 AM, Hall A
Discussion: 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: Lenz
Abstract: #3521
Poster
Session: Gastrointestinal (Colorectal) Cancer
Monday, 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: Atkins
Abstract: #9533
Poster
Session: Melanoma/Skin Cancers
Monday, 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:
Mantia
Abstract: #9550
Poster Session: Melanoma/Skin Cancers
Monday,
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:
Schadendorf
Abstract: #9551
Poster Session: Melanoma/Skin
Cancers
Monday, 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:
Taylor
Abstract: #9568
Poster Session: Melanoma/Skin Cancers
Monday,
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: Mandala
Abstract: #9584
Poster
Session: Melanoma/Skin Cancers
Monday, 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: Tawbi
Abstract: #9501
Oral
Session: Melanoma/Skin Cancers
Tuesday, June 4, 9:45 AM-12:45 PM,
S406
Presentation: 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:
McDermott
Abstract: #4513
Poster Discussion Session:
Genitourinary (Nonprostate) Cancer
Monday, June 3, Poster
Display: 1:15-4:15 PM, Hall A
Discussion: 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:
Emamekhoo
Abstract: #4517
Poster Discussion Session:
Genitourinary (Nonprostate) Cancer
Monday, June 3, Poster
Display: 1:15-4:15 PM, Hall A
Discussion: 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: Escudier
Abstract: #4575
Poster
Session: Genitourinary (Nonprostate) Cancer
Monday, 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:
Regan
Abstract: #4566
Poster Session: Genitourinary
(Nonprostate) Cancer
Monday, 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-Radtke
Abstract: #4524
Poster Session: Genitourinary
(Nonprostate) Cancer
Monday, 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:
Kirkwood
Abstract: #e14144
Online Only
Translational Medicine and Biomarkers
-
Serum IL-6 and CRP as prognostic factors in melanoma patients
receiving single agent and combination checkpoint inhibition
Author:
Weber
Abstract: #100
Clinical Science Symposium: Fine-Tuning
Checkpoint Inhibition: Biomarkers of Response and Resistance
Saturday,
June 1, Clinical Science Symposium: 8-9:30 AM, Hall D1
Presentation:
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: Wang
Abstract: #2544
Poster
Session: Developmental Immunotherapy and Tumor Immunobiology
Saturday,
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:
Szabo
Abstract: #2593
Poster Session: Developmental
Immunotherapy and Tumor Immunobiology
Saturday, 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: Szabo
Abstract:
#2594
Poster Session: Developmental Immunotherapy and Tumor
Immunobiology
Saturday, 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: Pignon
Abstract: #4568
Poster
Session: Genitourinary (Nonprostate) Cancer
Monday, 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: Hurwitz
Abstract:
#2623
Poster Session: Developmental Immunotherapy and Tumor
Immunobiology
Saturday, 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: Feeney
Abstract:
#TPS4143
Poster Session: Gastrointestinal (Noncolorectal) Cancer
Monday,
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: Khushalani
Abstract:
#TPS9601
Poster Session: Melanoma/Skin Cancers
Monday, 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: Tannir
Abstract: #TPS4595
Poster
Session: Genitourinary (Nonprostate) Cancer
Monday, 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:
Sonpavde
Abstract: #TPS4587
Poster Session: Genitourinary
(Nonprostate) Cancer
Monday, 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: Brahmer
Abstract: #9093
Poster
Session: Lung Cancer-Non-Small Cell Metastatic
Sunday, 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: Middleton
Abstract: #TPS2671
Poster
Session: Developmental Immunotherapy and Tumor Immunobiology
Saturday,
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:
Malhotra
Abstract: #8516
Poster Session: Lung
Cancer-Non-Small Cell Local-Regional/Small Cell/Other Thoracic Cancers
Sunday,
June 2, Poster Display: 8-11 AM; Hall A
Discussion: 11:15
AM–12:45 PM, S406
24
th
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-Domènech
Abstract: #S821
Oral Session: Hodgkin
lymphoma – Clinical
Saturday, June 15, 11:30 AM-12:45 PM, Hall 5
Presentation:
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:
LeBlanc
Abstract: #S822
Oral Session: Hodgkin lymphoma –
Clinical
Saturday, June 15, 11:30 AM-12:45 PM, Hall 5
Presentation:
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: Zinzani
Abstract:
#S1601
Oral Session: Aggressive lymphomas – First line,
combination therapy and real-life data
Sunday, June 16, 8-9:15
AM, Hall 5
Presentation: 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:
Dimopoulos
Abstract: #PS1370
Poster Session: Myeloma and
other monoclonal gammopathies – Clinical
Saturday, June 15,
5:30-7 PM, Poster Area
-
Investigating Mechanisms of Elotuzumab and Lenalidomide in Multiple
Myeloma
Author: Richardson
Abstract: #PF568
Poster
Session: Myeloma and other monoclonal gammopathies – Biology &
Translational Research
Friday, 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:
Moreau
Abstract: #PS1405
Poster Session: Myeloma and other
monoclonal gammopathies – Clinical
Saturday, 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:
Saglio
Abstract: #PF405
Poster Session: Chronic myeloid
leukemia – Clinical
Friday, 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: Shah
Abstract: #PF408
Poster
Session: Chronic myeloid leukemia – Clinical
Friday, 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:
Patterson
Abstract: #PF416
Poster Session: Chronic myeloid
leukemia – Clinical
Friday, 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: Cortes
Abstract:
#PS1181
Poster Session: Chronic myeloid leukemia – Clinical
Saturday,
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,
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and Facebook.
Bristol-Myers Squibb Forward-Looking Statement
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meaning of the Private Securities Litigation Reform Act of 1995
regarding the research, development and commercialization of
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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
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Bristol-Myers Squibb Company Media Inquiries: Ken Dominski609-302-3114 ken.dominski@bms.com Investors: Tim Power609-252-7509 timothy.power@bms.com