New data from our multiple myeloma portfolio
across targets and molecular approaches show significant progress
toward our goal of transforming the treatment paradigm and
improving outcomes for patients
Multiple first disclosures including
preliminary Phase 1 data for subcutaneous administration of
bispecific T cell engager alnuctamab in heavily pretreated multiple
myeloma, preliminary Phase 1 results for GPRC5D CAR T in
relapsed/refractory multiple myeloma and first results from the
Phase 2 KarMMa-2 trial evaluating Abecma in high-risk multiple
myeloma
New data for CD19-directed CAR T cell therapy
Breyanzi, including longer-term follow up from pivotal Phase 3
TRANSFORM study in second-line relapsed or refractory large B-cell
lymphoma
Bristol Myers Squibb (NYSE: BMY) today announced the
presentation of research across its hematology portfolio at the
64th American Society of Hematology (ASH) Annual Meeting and
Exposition, which will take place in New Orleans, Louisiana, and
virtually, from December 10 to 13, 2022. Data from more than 100
company-sponsored studies will be featured, including 34 oral
presentations, highlighting the range of modalities, targets and
research platforms the company is advancing and showcasing our
commitment to scientific progress across hematologic diseases.
“Our presence at ASH underscores the transformational potential
of our diverse pipeline, poised to deliver the next wave of
advances in hematology,” said Samit Hirawat, M.D., executive vice
president, chief medical officer, Global Drug Development, Bristol
Myers Squibb. “These exciting data, spanning a variety of
modalities and targets, demonstrate significant progress toward our
goals of improving long-term outcomes across patient populations
and finding solutions in important areas of remaining need.”
Key data being presented by Bristol Myers Squibb and its
partners at the 2022 ASH Annual Meeting and Exposition
include:
Cell Therapy
- Updated data including longer-term follow up from the primary
analysis of the Phase 3 TRANSFORM study evaluating Breyanzi®
(lisocabtagene maraleucel) versus the standard of care as a
second-line treatment in relapsed or refractory large B-cell
lymphoma (LBCL)
- Updated data from the primary analysis of the Phase 2 OUTREACH
study evaluating Breyanzi as a third-line plus treatment in
relapsed or refractory LBCL in the community setting
- Safety and efficacy results of the match-adjusted indirect
comparison of the TRANSFORM versus ZUMA-7 studies evaluating
Breyanzi versus axicabtagene ciloleucel in the second-line setting
in relapsed or refractory LBCL
- Two first disclosures of results from cohorts 2a and 2c of the
Phase 2 KarMMa-2 trial evaluating Abecma in high-risk multiple
myeloma
- First disclosure of preliminary Phase 1 results for GPRC5D
chimeric antigen receptor (CAR) T cell therapy in patients with
relapsed/refractory (R/R) multiple myeloma, including patients
previously treated with a B-cell maturation antigen (BCMA)-directed
CAR T cell therapy
Hematology
- Multiple analyses of Reblozyl® (luspatercept-aamt), including
overall survival data from the Phase 3 MEDALIST study in lower-risk
myelodysplastic syndromes and real-world, longer-term results from
the Phase 2 BEYOND study in beta thalassemia
- Multiple analyses of Inrebic® (fedratinib), including the
primary analysis of safety and efficacy from the Phase 3b FREEDOM
trial in intermediate- or high-risk myelofibrosis
- Longitudinal analyses of acute myeloid leukemia gene mutations
with Onureg® (azacitidine tablets) from the Phase 3 QUAZAR® AML-001
study
Early Pipeline
- First disclosure of preliminary results from the dose
escalation and expansion components of the Phase 1 CC-93269 MM-001
study, evaluating subcutaneous bispecific T cell engager alnuctamab
in heavily pretreated multiple myeloma
- First results from dose expansion cohort of the CC-92480 Phase
1/2 MM-001 study, evaluating CELMoDTM agent mezigdomide with
dexamethasone in patients with R/R multiple myeloma
- Results from post-BCMA cohort of the CC-220 Phase 1/2 MM-001
study, evaluating CELMoD agent iberdomide with dexamethasone in
patients with R/R multiple myeloma previously treated with a
BCMA-directed therapy
- First results from a Phase 1/2 study evaluating BMS-986158, a
potent Bromodomain and Extraterminal (BET) inhibitor, as
monotherapy and in combination with ruxolitinib or Inrebic in
intermediate- or high-risk myelofibrosis
To learn more about our science and commitment in hematology,
check out the BMS at ASH 2022 content hub. You can find additional
information about BMS’ presence at the meeting on the ASH
website.
Selected Bristol Myers Squibb studies at the 64th ASH Annual
Meeting and Exposition include:
Abstract Title
Author
Presentation Type/#
Session Title
Session Date/Time (CST)
Beta Thalassemia
Erythroid Response in Patients with
Non-Transfusion-Dependent ß-Thalassemia Treated with Luspatercept:
Long-Term Data from the BEYOND Trial
Ali Taher
Poster
Presentation #3669
112. Thalassemia and Globin Gene
Regulation: Poster III
Monday, December 12, 6:00 – 8:00 PM
Lymphoma
Five-Year Results From the Phase 3
Randomized Study AUGMENT: Lenalidomide Plus Rituximab (R2) vs
Rituximab Plus Placebo in Patients with Relapsed/Refractory
Indolent Non-Hodgkin Lymphoma
John Leonard
Oral
Presentation
#230
623. Mantle Cell, Follicular, and Other
Indolent B Cell Lymphomas: Clinical and Epidemiological III
Saturday,
December 10, 2:15 PM
Iberdomide (CC-220) Monotherapy or in
Combination with an Anti-CD20 Monoclonal Antibody as Effective
Therapy in Patients with Relapsed/Refractory Lymphoma: Early
Results from a Phase 1/2 Study
Catherine Thieblemont
Oral
Presentation #233
623. Mantle Cell, Follicular, and Other
Indolent B Cell Lymphomas: Clinical and Epidemiological III
Saturday, December 10, 3:00 PM
Lisocabtagene Maraleucel (liso-cel) versus
Standard of Care (SOC) with Salvage Chemotherapy Followed by
Autologous Stem Cell Transplantation (ASCT) as Second-line (2L)
Treatment in Patients with Relapsed or Refractory Large B-Cell
Lymphoma (LBCL): Primary Analysis of the Randomized, Phase 3
TRANSFORM Study
Jeremy Abramson
Oral
Presentation #655
705. Cellular Immunotherapies: Results
from CD19-Directed CAR T in treating Aggressive B-cell
Lymphomas
Sunday, December 11, 4:30 PM
Matching-Adjusted Indirect Comparison
(MAIC) of Lisocabtagene Maraleucel (Liso-cel) Versus Axicabtagene
Ciloleucel (Axi-cel) for Second-line (2L) Treatment of Patients
with Refractory/Early Relapsed (R/R) Large B-Cell Lymphoma
(LBCL)
Jeremy Abramson
Poster
Presentation #2031
705. Cellular Immunotherapies: Late Phase
and Commercially Available Therapies: Poster I
Saturday December 10, 5:30 – 7:30 PM
Real-World Treatment Patterns and Costs of
Chimeric Antigen Receptor (CAR) T Cell Therapies (CAR T),
Polatuzumab Vedotin-piiq (pola), and Tafasitamab-cxix (tafa) in
Relapsed or Refractory (R/R) Diffuse Large B-Cell Lymphoma
(DLBCL)
Fei Fei Liu
Oral
Presentation #999
905. Outcomes Research—Lymphoid
Malignancies: Health Outcomes in CAR T and Stem Cell
Transplantation
Monday, December 12, 5:00 PM
Results from OUTREACH: A Phase 2 Study of
Lisocabtagene Maraleucel (Liso-cel) Administered as Outpatient
(Outpt) or Inpatient (Inpt) Treatment in the
Community/Nonuniversity Setting in Patients (Pts) with Relapsed or
Refractory (R/R) Large B-Cell Lymphoma (LBCL)
Yuliya
Linhares
Poster
Presentation #4673
705. Cellular Immunotherapies: Late Phase
and Commercially Available Therapies: Poster III
Monday, December 12, 6:00 – 8:00 PM
Multiple Myeloma
Alnuctamab (BMS-986349; CC-93269), a
B-cell Maturation Antigen (BCMA) x CD3 2+1 T cell Engager (TCE), in
Patients (pts) with Relapsed/Refractory Multiple Myeloma (RRMM):
Results from a Phase 1 First-in-Human Clinical Study
Sandy W. Wong
Oral
Presentation #162
653. Myeloma and Plasma Cell Dyscrasias:
Prospective Therapeutic Trials: Bispecific Monoclonal Antibodies in
Myeloma
Saturday, December 10, 1:15 PM
KarMMa-2 Cohort 2a: Efficacy and Safety of
Idecabtagene Vicleucel in Clinical High-risk Multiple Myeloma
Patients with Early Relapse After Frontline Autologous Stem Cell
Transplantation
Saad Usmani
Oral
Presentation #361
704. Cellular Immunotherapies: Early Phase
and Investigational Therapies: CAR T in Multiple Myeloma and T-cell
Therapies After Allo-HCT
Saturday, December 10, 4:00 PM
Clinical Activity of BMS-986393
(CC-95266), a G Protein–Coupled Receptor Class C Group 5 Member D
(GPRC5D)–Targeted Chimeric Antigen Receptor (CAR) T Cell Therapy,
in Patients With Relapsed and/or Refractory (R/R) Multiple Myeloma
(MM): First Results From a Phase 1, Multicenter, Open-Label
Study
Susan Bal
Oral
Presentation #364
704. Cellular Immunotherapies: Early Phase
and Investigational Therapies: CAR T in Multiple Myeloma and T-cell
Therapies After Allo-HCT
Saturday, December 10, 4:45 PM
Iberdomide (IBER) in Combination with
Dexamethasone (DEX) in Relapsed/Refractory Multiple Myeloma (RRMM):
Results from the Anti-B-Cell Maturation Antigen (BCMA)-Exposed
Cohort of the CC-220-MM-001 Trial
Sagar Lonial
Poster
Presentation #1918
653. Myeloma and Plasma Cell Dyscrasias:
Prospective Therapeutic Trials: Poster I
Saturday, December 10, 5:30 – 7:30 PM
Results From the First Phase 1 Clinical
Study of the B-cell Maturation Antigen (BCMA) NEX-T Chimeric
Antigen Receptor (CAR) T Cell Therapy CC-98633/BMS-986354 in
Patients (pts) with Relapsed/Refractory Multiple Myeloma (RRMM)
Luciano Megala Costa
Oral
Presentation #566
653. Myeloma and Plasma Cell Dyscrasias:
Prospective Therapeutic Trials: Novel Drugs and Optimized
Approaches in Myeloma
Sunday, December 11, 12:15 PM
Mezigdomide (CC-92480), a Potent, Novel
Cereblon E3 Ligase Modulator (CELMoD), Combined with Dexamethasone
(DEX) in Patients (pts) with Relapsed/Refractory Multiple Myeloma
(RRMM): Preliminary Results from the Dose-Expansion Phase of the
CC-92480-MM-001 Trial
Paul Richardson
Oral
Presentation #568
653. Myeloma and Plasma Cell Dyscrasias:
Prospective Therapeutic Trials: Novel Drugs and Optimized
Approaches in Myeloma
Sunday, December 11, 12:45 PM
KarMMa-2 Cohort 2c: Efficacy and Safety of
Idecabtagene Vicleucel in Patients with Clinical High-risk Multiple
Myeloma due to Inadequate Response to Frontline Autologous Stem
Cell Transplantation
Madhav Dhodapkar
Poster
Presentation #3314
704. Cellular Immunotherapies: Early Phase
and Investigational Therapies: Poster II
Sunday, December 11, 6:00 – 8:00 PM
Myelodysplastic Syndromes
Real-World Outcomes of Patients with
Lower-Risk Myelodysplastic Syndromes (LR-MDS) Treated with
Luspatercept: an Evaluation of US Clinical Practice Utilization and
Treatment Patterns
Sudipto Mukherjee
Oral
Presentation #389
906. Outcomes Research—Myeloid
Malignancies I
Saturday, December 10, 5:00 PM
Multiple Episodes of Transfusion
Independence with Luspatercept Treatment and the Impact of Dose
Escalation in Patients with Lower-Risk Myelodysplastic Syndromes
from the MEDALIST Study
Uwe Platzbecker
Poster
Presentation #3098
637. Myelodysplastic Syndromes – Clinical
and Epidemiological: Poster II
Sunday, December 11, 6:00 – 8:00 PM
Overall Survival and Progression-Free
Survival of Patients Following Luspatercept Treatment in the
MEDALIST Trial
Valeria Santini
Poster Presentation #1174
637. Myelodysplastic Syndromes – Clinical
and Epidemiological: Poster I
Sunday, December 11, 5:30 – 7:30 PM
Myelofibrosis
Safety and Efficacy of Fedratinib in
Patients with Primary (P), Post-Polycythemia Vera (post-PV), and
Post-Essential Thrombocythemia (Post-ET) Myelofibrosis (MF)
Previously Treated with Ruxolitinib: Primary Analysis of the
FREEDOM Trial
Vikas Gupta
Poster Presentation #1711
634. Myeloproliferative Syndromes:
Clinical and Epidemiological: Poster I
Saturday, December 10, 5:30 – 7:30 PM
BMS-986158, a Potent BET Inhibitor, As
Monotherapy and in Combination with Ruxolitinib or Fedratinib in
Intermediate- or High-Risk Myelofibrosis: First Results from a
Phase 1/2 Study
Rosa Ayala
Poster
Presentation
#4346
634. Myeloproliferative Syndromes:
Clinical and Epidemiological: Poster III
Monday, December 12, 6:00 – 8:00 PM
Bristol Myers Squibb: Creating a Better
Future for Cancer Patients
Bristol Myers Squibb is inspired by a single vision —
transforming patients’ lives through science. The goal of the
company’s cancer research is to deliver medicines that offer each
patient a better, healthier life and to make cure a possibility.
Building on a legacy across a broad range of cancers that have
changed survival expectations for many, Bristol Myers Squibb
researchers are exploring new frontiers in personalized medicine,
and through innovative digital platforms, are turning data into
insights that sharpen their focus. Deep scientific expertise,
cutting-edge capabilities and discovery platforms enable the
company to look at cancer from every angle. Cancer can have a
relentless grasp on many parts of a patient’s life, and Bristol
Myers Squibb is committed to taking actions to address all aspects
of care, from diagnosis to survivorship. Because as a leader in
cancer care, Bristol Myers Squibb is working to empower all people
with cancer to have a better future.
BREYANZI U.S. INDICATION
Breyanzi is a CD-19 directed chimeric antigen receptor (CAR) T
cell therapy, administered as a defined composition to reduce
variability of the CD8 and CD4 component dose. Breyanzi has a 4-1BB
costimulatory domain which enhances the expansion and persistence
of the CAR T cells. Breyanzi was previously approved by the U.S.
Food and Drug Administration for the treatment of adult patients
with relapsed or refractory LBCL after two or more lines of
systemic therapy, including diffuse large B-cell lymphoma (DLBCL)
not otherwise specified (including DLBCL arising from indolent
lymphoma), high-grade B-cell lymphoma, primary mediastinal large
B-cell lymphoma, and follicular lymphoma grade 3B. Breyanzi is
available only through a restricted program under a Risk Evaluation
and Mitigation Strategy (REMS) called the BREYANZI REMS.
Breyanzi is also approved in Europe, Switzerland, Canada and
Japan for relapsed and refractory LBCL after two or more lines of
systemic therapy. Bristol Myers Squibb’s clinical development
program for Breyanzi includes clinical studies in earlier lines of
treatment for patients with relapsed or refractory LBCL and other
types of lymphoma. For more information, visit
clinicaltrials.gov.
IMPORTANT SAFETY
INFORMATION
BOXED WARNING: CYTOKINE RELEASE SYNDROME and NEUROLOGIC
TOXICITIES
- Cytokine Release Syndrome (CRS), including fatal or
life-threatening reactions, occurred in patients receiving
BREYANZI. Do not administer BREYANZI to patients with active
infection or inflammatory disorders. Treat severe or
life-threatening CRS with tocilizumab with or without
corticosteroids.
- Neurologic toxicities, including fatal or life-threatening
reactions, occurred in patients receiving BREYANZI, including
concurrently with CRS, after CRS resolution or in the absence of
CRS. Monitor for neurologic events after treatment with BREYANZI.
Provide supportive care and/or corticosteroids as needed.
- BREYANZI is available only through a restricted program under a
Risk Evaluation and Mitigation Strategy (REMS) called the BREYANZI
REMS.
Cytokine Release Syndrome
Cytokine release syndrome (CRS), including fatal or
life-threatening reactions, occurred following treatment with
BREYANZI. Among patients receiving BREYANZI for LBCL (N=418), CRS
occur in 46% (190/418) of patients, including ≥ Grade 3 CRS (Lee
grading system) in 3.1% of patients.
In patients receiving BREYANZI after two or more lines of
therapy for LBCL, CRS occurred in 46% (122/268), including ≥ Grade
3 CRS in 4.1% of patients. One patient had fatal CRS and 2 had
ongoing CRS at time of death. The median time to onset was 5 days
(range: 1 to 15 days). CRS resolved in 98% with a median duration
of 5 days (range: 1 to 17 days).
In patients receiving BREYANZI after one line of therapy for
LBCL, CRS occurred in 45% (68/150), including Grade 3 CRS in 1.3%
of patients. The median time to onset was 4 days (range: 1 to 63
days). CRS resolved in all patients with a median duration of 4
days (range: 1 to 16 days).
The most common manifestations of CRS (≥10%) included fever
(94%), hypotension (42%), tachycardia (28%), chills (23%), hypoxia
(16%), and headache (12%).
Serious events that may be associated with CRS include cardiac
arrhythmias (including atrial fibrillation and ventricular
tachycardia), cardiac arrest, cardiac failure, diffuse alveolar
damage, renal insufficiency, capillary leak syndrome, hypotension,
hypoxia, and hemophagocytic lymphohistiocytosis/macrophage
activation syndrome (HLH/MAS).
Ensure that 2 doses of tocilizumab are available prior to
infusion of BREYANZI.
Of the 418 patients who received BREYANZI for LBCL, 23% received
tocilizumab and/or a corticosteroid for CRS, including 10% who
received tocilizumab only and 2.2% who received corticosteroids
only.
Neurologic Toxicities
Neurologic toxicities that were fatal or life-threatening,
including immune effector cell-associated neurotoxicity syndrome
(ICANS), occurred following treatment with BREYANZI. Serious events
including cerebral edema and seizures occurred with BREYANZI. Fatal
and serious cases of leukoencephalopathy, some attributable to
fludarabine, also occurred.
In patients receiving BREYANZI after two or more lines of
therapy for LBCL, CAR T cell-associated neurologic toxicities
occurred in 35% (95/268), including ≥ Grade 3 in 12% of patients.
Three patients had fatal neurologic toxicity and 7 had ongoing
neurologic toxicity at time of death. The median time to onset of
neurotoxicity was 8 days (range: 1 to 46 days). Neurologic
toxicities resolved in 85% with a median duration of 12 days
(range: 1 to 87 days).
In patients receiving BREYANZI after one line of therapy for
LBCL, CAR T cell-associated neurologic toxicities occurred in 27%
(41/150) of patients, including Grade 3 cases in 7% of patients.
The median time to onset of neurologic toxicities was 8 days
(range: 1 to 63 days). The median duration of neurologic toxicity
was 6 days (range: 1 to 119 days).
In all patients combined receiving BREYANZI for LBCL, neurologic
toxicities occurred in 33% (136/418), including ≥ Grade 3 cases in
10% of patients. The median time to onset was 8 days (range: 1 to
63), with 87% of cases developing by 16 days. Neurologic toxicities
resolved in 85% of patients with a median duration of 11 days
(range: 1 to 119 days). Of patients developing neurotoxicity, 77%
(105/136) also developed CRS.
The most common neurologic toxicities (≥ 5%) included
encephalopathy (20%), tremor (13%), aphasia (8%), headache (6%),
dizziness (6%), and delirium (5%).
CRS and Neurologic Toxicities Monitoring
Monitor patients daily for at least 7 days following BREYANZI
infusion at a REMS-certified healthcare facility for signs and
symptoms of CRS and neurologic toxicities and assess for other
causes of neurological symptoms. Monitor patients for signs and
symptoms of CRS and neurologic toxicities for at least 4 weeks
after infusion and treat promptly. At the first sign of CRS,
institute treatment with supportive care, tocilizumab, or
tocilizumab and corticosteroids as indicated. Manage neurologic
toxicity with supportive care and/or corticosteroid as needed.
Counsel patients to seek immediate medical attention should signs
or symptoms of CRS or neurologic toxicity occur at any time.
BREYANZI REMS
Because of the risk of CRS and neurologic toxicities, BREYANZI
is available only through a restricted program under a Risk
Evaluation and Mitigation Strategy (REMS) called the BREYANZI REMS.
The required components of the BREYANZI REMS are:
- Healthcare facilities that dispense and administer BREYANZI
must be enrolled and comply with the REMS requirements.
- Certified healthcare facilities must have on-site, immediate
access to tocilizumab.
- Ensure that a minimum of 2 doses of tocilizumab are available
for each patient for infusion within 2 hours after BREYANZI
infusion, if needed for treatment of CRS.
- Certified healthcare facilities must ensure that healthcare
providers who prescribe, dispense, or administer BREYANZI are
trained on the management of CRS and neurologic toxicities.
Further information is available at www.BreyanziREMS.com, or
contact Bristol-Myers Squibb at 1-888-423-5436.
Hypersensitivity Reactions
Allergic reactions may occur with the infusion of BREYANZI.
Serious hypersensitivity reactions, including anaphylaxis, may be
due to dimethyl sulfoxide (DMSO).
Serious Infections
Severe infections, including life-threatening or fatal
infections, have occurred in patients after BREYANZI infusion.
In patients receiving BREYANZI for LBCL, infections of any grade
occurred in 36% with Grade 3 or higher infections occurring in 12%
of all patients. Grade 3 or higher infections with an unspecified
pathogen occurred in 7%, bacterial infections occurred in 4.3%,
viral infections in 1.9% and fungal infections in 0.5%.
Febrile neutropenia developed after BREYANZI infusion in 8% of
patients with LBCL. Febrile neutropenia may be concurrent with CRS.
In the event of febrile neutropenia, evaluate for infection and
manage with broad spectrum antibiotics, fluids, and other
supportive care as medically indicated.
Monitor patients for signs and symptoms of infection before and
after BREYANZI administration and treat appropriately. Administer
prophylactic antimicrobials according to standard institutional
guidelines.
Avoid administration of BREYANZI in patients with clinically
significant active systemic infections.
Viral reactivation: Hepatitis B virus (HBV) reactivation, in
some cases resulting in fulminant hepatitis, hepatic failure, and
death, can occur in patients treated with drugs directed against B
cells.
In patients who received BREYANZI for LBCL, 15 of the 16
patients with a prior history of HBV were treated with concurrent
antiviral suppressive therapy. Perform screening for HBV, HCV, and
HIV in accordance with clinical guidelines before collection of
cells for manufacturing. In patients with prior history of HBV,
consider concurrent antiviral suppressive therapy to prevent HBV
reactivation per standard guidelines.
Prolonged Cytopenias
Patients may exhibit cytopenias not resolved for several weeks
following lymphodepleting chemotherapy and BREYANZI infusion.
Grade 3 or higher cytopenias persisted at Day 29 following
BREYANZI infusion in 36% of patients with LBCL, and included
thrombocytopenia in 28%, neutropenia in 21%, and anemia in 6%.
Monitor complete blood counts prior to and after BREYANZI
administration.
Hypogammaglobulinemia
B-cell aplasia and hypogammaglobulinemia can occur in patients
receiving treatment with BREYANZI.
In patients receiving BREYANZI for LBCL, hypogammaglobulinemia
was reported as an adverse reaction in 11% of patients.
Hypogammaglobulinemia, either as an adverse reaction or laboratory
IgG level below 500 mg/dL after infusion, was reported in 28% of
patients.
Monitor immunoglobulin levels after treatment with BREYANZI and
manage using infection precautions, antibiotic prophylaxis, and
immunoglobulin replacement as clinically indicated.
Live vaccines: The safety of immunization with live viral
vaccines during or following BREYANZI treatment has not been
studied. Vaccination with live virus vaccines is not recommended
for at least 6 weeks prior to the start of lymphodepleting
chemotherapy, during BREYANZI treatment, and until immune recovery
following treatment with BREYANZI.
Secondary Malignancies
Patients treated with BREYANZI may develop secondary
malignancies. Monitor lifelong for secondary malignancies. In the
event that a secondary malignancy occurs, contact Bristol-Myers
Squibb at 1-888-805-4555 for reporting and to obtain instructions
on collection of patient samples for testing.
Effects on Ability to Drive and Use Machines
Due to the potential for neurologic events, including altered
mental status or seizures, patients receiving BREYANZI are at risk
for developing altered or decreased consciousness or impaired
coordination in the 8 weeks following BREYANZI administration.
Advise patients to refrain from driving and engaging in hazardous
occupations or activities, such as operating heavy or potentially
dangerous machinery, for at least 8 weeks.
Adverse Reactions
The most common nonlaboratory adverse reactions (incidence ≥
30%) are fever, CRS, fatigue, musculoskeletal pain, and nausea.
The most common Grade 3-4 laboratory abnormalities (≥ 30%)
include lymphocyte count decrease, neutrophil count decrease,
platelet count decrease, hemoglobin decrease.
Please see full Prescribing Information, including Boxed
WARNINGS and Medication Guide.
ABECMA U.S. INDICATION
ABECMA (idecabtagene vicleucel) is a B-cell maturation antigen
(BCMA)-directed genetically modified autologous T cell
immunotherapy indicated for the treatment of adult patients with
relapsed or refractory multiple myeloma after four or more prior
lines of therapy, including an immunomodulatory agent, a proteasome
inhibitor, and an anti-CD38 monoclonal antibody.
IMPORTANT SAFETY
INFORMATION
BOXED WARNING: CYTOKINE RELEASE SYNDROME, NEUROLOGIC
TOXICITIES, HLH/MAS, AND PROLONGED CYTOPENIA
- Cytokine Release Syndrome (CRS), including fatal or
life-threatening reactions, occurred in patients following
treatment with ABECMA. Do not administer ABECMA to patients with
active infection or inflammatory disorders. Treat severe or
life-threatening CRS with tocilizumab or tocilizumab and
corticosteroids.
- Neurologic Toxicities, which may be severe or life-threatening,
occurred following treatment with ABECMA, including concurrently
with CRS, after CRS resolution, or in the absence of CRS. Monitor
for neurologic events after treatment with ABECMA. Provide
supportive care and/or corticosteroids as needed.
- Hemophagocytic Lymphohistiocytosis/Macrophage Activation
Syndrome (HLH/MAS) including fatal and life-threatening reactions,
occurred in patients following treatment with ABECMA. HLH/MAS can
occur with CRS or neurologic toxicities.
- Prolonged Cytopenia with bleeding and infection, including
fatal outcomes following stem cell transplantation for
hematopoietic recovery, occurred following treatment with
ABECMA.
- ABECMA is available only through a restricted program under a
Risk Evaluation and Mitigation Strategy (REMS) called the ABECMA
REMS.
Cytokine Release Syndrome (CRS): CRS, including fatal or
life-threatening reactions, occurred following treatment with
ABECMA. CRS occurred in 85% (108/127) of patients receiving ABECMA.
Grade 3 or higher CRS (Lee grading system) occurred in 9% (12/127)
of patients, with Grade 5 CRS reported in one (0.8%) patient. The
median time to onset of CRS, any grade, was 1 day (range: 1 - 23
days) and the median duration of CRS was 7 days (range: 1 - 63
days) in all patients including the patient who died. The most
common manifestations of CRS included pyrexia (98%), hypotension
(41%), tachycardia (35%), chills (31%), hypoxia (20%), fatigue
(12%), and headache (10%). Grade 3 or higher events that may be
associated with CRS include hypotension, hypoxia,
hyperbilirubinemia, hypofibrinogenemia, acute respiratory distress
syndrome (ARDS), atrial fibrillation, hepatocellular injury,
metabolic acidosis, pulmonary edema, multiple organ dysfunction
syndrome and HLH/MAS.
Identify CRS based on clinical presentation. Evaluate for and
treat other causes of fever, hypoxia, and hypotension. CRS has been
reported to be associated with findings of HLH/MAS, and the
physiology of the syndromes may overlap. HLH/MAS is a potentially
life-threatening condition. In patients with progressive symptoms
of CRS or refractory CRS despite treatment, evaluate for evidence
of HLH/MAS.
Fifty four percent (68/127) of patients received tocilizumab;
35% (45/127) received a single dose while 18% (23/127) received
more than 1 dose of tocilizumab. Overall, across the dose levels,
15% (19/127) of patients received at least 1 dose of
corticosteroids for treatment of CRS. All patients that received
corticosteroids for CRS received tocilizumab.
Overall rate of CRS was 79% and rate of Grade 2 CRS was 23% in
patients treated in the 300 x 106 CAR+ T cell dose cohort. For
patients treated in the 450 x 106 CAR+ T cell dose cohort, the
overall rate of CRS was 96% and rate of Grade 2 CRS was 40%. Rate
of Grade 3 or higher CRS was similar across the dose range. The
median duration of CRS for the 450 x 106 CAR+ T cell dose cohort
was 7 days (range: 1-63 days) and for the 300 x 106 CAR+ T cell
dose cohort was 6 days (range: 2-28 days). In the 450 x 106 CAR+ T
cell dose cohort, 68% (36/53) of patients received tocilizumab and
23% (12/53) received at least 1 dose of corticosteroids for
treatment of CRS. In the 300 x 106 CAR+ T cell dose cohort, 44%
(31/70) of patients received tocilizumab and 10% (7/70) received
corticosteroids. All patients that received corticosteroids for CRS
also received tocilizumab. Ensure that a minimum of 2 doses of
tocilizumab are available prior to infusion of ABECMA.
Monitor patients at least daily for 7 days following ABECMA
infusion at the REMS-certified healthcare facility for signs and
symptoms of CRS. Monitor patients for signs or symptoms of CRS for
at least 4 weeks after infusion. At the first sign of CRS,
institute treatment with supportive care, tocilizumab and/or
corticosteroids as indicated.
Counsel patients to seek immediate medical attention should
signs or symptoms of CRS occur at any time.
Neurologic Toxicities: Neurologic toxicities, which may
be severe or life-threatening, occurred following treatment with
ABECMA, including concurrently with CRS, after CRS resolution, or
in the absence of CRS. CAR T cell-associated neurotoxicity occurred
in 28% (36/127) of patients receiving ABECMA, including Grade 3 in
4% (5/127) of patients. One patient had ongoing Grade 2
neurotoxicity at the time of death. Two patients had ongoing Grade
1 tremor at the time of data cutoff. The median time to onset of
neurotoxicity was 2 days (range: 1 - 42 days). CAR T
cell-associated neurotoxicity resolved in 92% (33/36) of patients
with a median duration of neurotoxicity was 5 days (range: 1 - 61
days). The median duration of neurotoxicity was 6 days (range: 1 -
578) in all patients including those with ongoing neurotoxicity at
the time of death or data cut off. Thirty-four patients with
neurotoxicity had CRS. Neurotoxicity had onset in 3 patients
before, 29 patients during, and 2 patients after CRS. The rate of
Grade 3 neurotoxicity was 8% in the 450 x 106 CAR+ T cell dose
cohort and 1.4% in the 300 x 106 CAR+ T cell dose cohort. The most
frequently reported (greater than or equal to 5%) manifestations of
CAR T cell-associated neurotoxicity include encephalopathy (20%),
tremor (9%), aphasia (7%), and delirium (6%). Grade 4 neurotoxicity
and cerebral edema in 1 patient has been reported with ABECMA in
another study in multiple myeloma. Grade 3 myelitis and Grade 3
parkinsonism have been reported after treatment with ABECMA in
another study in multiple myeloma.
Monitor patients at least daily for 7 days following ABECMA
infusion at the REMS-certified healthcare facility for signs and
symptoms of neurologic toxicities. Rule out other causes of
neurologic symptoms. Monitor patients for signs or symptoms of
neurologic toxicities for at least 4 weeks after infusion and treat
promptly. Neurologic toxicity should be managed with supportive
care and/or corticosteroids as needed.
Counsel patients to seek immediate medical attention should
signs or symptoms of neurologic toxicity occur at any time.
Hemophagocytic Lymphohistiocytosis (HLH)/Macrophage
Activation Syndrome (MAS): HLH/MAS occurred in 4% (5/127) of
patients receiving ABECMA. One patient treated in the 300 x 106
CAR+ T cell dose cohort developed fatal multi-organ HLH/MAS with
CRS. In another patient with fatal bronchopulmonary aspergillosis,
HLH/MAS was contributory to the fatal outcome. Three cases of Grade
2 HLH/MAS resolved. The rate of HLH/MAS was 8% in the 450 x 106
CAR+ T cell dose cohort and 1% in the 300 x 106 CAR+ T cell dose
cohort. All events of HLH/MAS had onset within 10 days of receiving
ABECMA with a median onset of 7 days (range: 4-9 days) and occurred
in the setting of ongoing or worsening CRS. Two patients with
HLH/MAS had overlapping neurotoxicity. The manifestations of
HLH/MAS include hypotension, hypoxia, multiple organ dysfunction,
renal dysfunction, and cytopenia. HLH/MAS is a potentially
life-threatening condition with a high mortality rate if not
recognized early and treated. Treatment of HLH/MAS should be
administered per institutional standards.
ABECMA REMS: Due to the risk of CRS and neurologic
toxicities, ABECMA is available only through a restricted program
under a Risk Evaluation and Mitigation Strategy (REMS) called the
ABECMA REMS. Further information is available at www.AbecmaREMS.com
or 18884235436.
Hypersensitivity Reactions: Allergic reactions may occur
with the infusion of ABECMA. Serious hypersensitivity reactions,
including anaphylaxis, may be due to dimethyl sulfoxide (DMSO) in
ABECMA.
Infections: ABECMA should not be administered to patients
with active infections or inflammatory disorders. Severe,
life-threatening, or fatal infections occurred in patients after
ABECMA infusion. Infections (all grades) occurred in 70% of
patients. Grade 3 or 4 infections occurred in 23% of patients.
Overall, 4 patients had Grade 5 infections (3%); 2 patients (1.6%)
had Grade 5 events of pneumonia, 1 patient (0.8%) had Grade 5
bronchopulmonary aspergillosis, and 1 patient (0.8%) had
cytomegalovirus (CMV) pneumonia associated with Pneumocystis
jirovecii. Monitor patients for signs and symptoms of infection
before and after ABECMA infusion and treat appropriately.
Administer prophylactic, preemptive, and/or therapeutic
antimicrobials according to standard institutional guidelines.
Febrile neutropenia was observed in 16% (20/127) of patients
after ABECMA infusion and may be concurrent with CRS. In the event
of febrile neutropenia, evaluate for infection and manage with
broad spectrum antibiotics, fluids, and other supportive care as
medically indicated.
Viral Reactivation: Cytomegalovirus (CMV) infection resulting in
pneumonia and death has occurred following ABECMA administration.
Monitor and treat for CMV reactivation in accordance with clinical
guidelines. Hepatitis B virus (HBV) reactivation, in some cases
resulting in fulminant hepatitis, hepatic failure, and death, can
occur in patients treated with drugs directed against plasma cells.
Perform screening for CMV, HBV, hepatitis C virus (HCV), and human
immunodeficiency virus (HIV) in accordance with clinical guidelines
before collection of cells for manufacturing.
Prolonged Cytopenias: Patients may exhibit prolonged
cytopenias following lymphodepleting chemotherapy and ABECMA
infusion. In the KarMMa study, 41% of patients (52/127) experienced
prolonged Grade 3 or 4 neutropenia and 49% (62/127) experienced
prolonged Grade 3 or 4 thrombocytopenia that had not resolved by
Month 1 following ABECMA infusion. Rate of prolonged neutropenia
was 49% in the 450 x 106 CAR+ T cell dose cohort and 34% in the 300
x 106 CAR+ T cell dose cohort. In 83% (43/52) of patients who
recovered from Grade 3 or 4 neutropenia after Month 1, the median
time to recovery from ABECMA infusion was 1.9 months. In 65%
(40/62) of patients who recovered from Grade 3 or 4
thrombocytopenia, the median time to recovery was 2.1 months.
Median time to cytopenia recovery was similar across the 300 and
450 x 106 dose cohort.
Three patients underwent stem cell therapy for hematopoietic
reconstitution due to prolonged cytopenia. Two of the three
patients died from complications of prolonged cytopenia. Monitor
blood counts prior to and after ABECMA infusion. Manage cytopenia
with myeloid growth factor and blood product transfusion support
according to institutional guidelines.
Hypogammaglobulinemia: Plasma cell aplasia and
hypogammaglobulinemia can occur in patients receiving treatment
with ABECMA. Hypogammaglobulinemia was reported as an adverse event
in 21% (27/127) of patients; laboratory IgG levels fell below 500
mg/dl after infusion in 25% (32/127) of patients treated with
ABECMA.
Monitor immunoglobulin levels after treatment with ABECMA and
administer IVIG for IgG <400 mg/dl. Manage per local
institutional guidelines, including infection precautions and
antibiotic or antiviral prophylaxis.
The safety of immunization with live viral vaccines during or
following ABECMA treatment has not been studied. Vaccination with
live virus vaccines is not recommended for at least 6 weeks prior
to the start of lymphodepleting chemotherapy, during ABECMA
treatment, and until immune recovery following treatment with
ABECMA.
Secondary Malignancies: Patients treated with ABECMA may
develop secondary malignancies. Monitor life-long for secondary
malignancies. If a secondary malignancy occurs, contact Bristol
Myers Squibb at 1-888-805-4555 to obtain instructions on patient
samples to collect for testing of secondary malignancy of T cell
origin.
Effects on Ability to Drive and Operate Machinery: Due to
the potential for neurologic events, including altered mental
status or seizures, patients receiving ABECMA are at risk for
altered or decreased consciousness or coordination in the 8 weeks
following ABECMA infusion. Advise patients to refrain from driving
and engaging in hazardous occupations or activities, such as
operating heavy or potentially dangerous machinery, during this
initial period.
Adverse Reactions: The most common nonlaboratory adverse
reactions (incidence greater than or equal to 20%) include CRS,
infections – pathogen unspecified, fatigue, musculoskeletal pain,
hypogammaglobulinemia, diarrhea, upper respiratory tract infection,
nausea, viral infections, encephalopathy, edema, pyrexia, cough,
headache, and decreased appetite.
Please see full Prescribing Information, including Boxed
WARNINGS and Medication Guide.
REBLOZYL U.S. INDICATION
Reblozyl, a first-in-class therapeutic option, promotes
late-stage red blood cell maturation in animal models. Reblozyl is
being developed and commercialized through a global collaboration
with Merck following Merck’s acquisition of Acceleron Pharma, Inc.
in November 2021. Reblozyl is currently approved in the U.S. for
the treatment of:
- anemia in adult patients with beta thalassemia who require
regular red blood cell transfusions, and
- anemia failing an erythropoiesis stimulating agent and
requiring 2 or more red blood cell units over 8 weeks in adult
patients with very low- to intermediate-risk myelodysplastic
syndrome with ring sideroblasts (MDS-RS) or with
myelodysplastic/myeloproliferative neoplasm with ring sideroblasts
and thrombocytosis (MDS/MPN-RS-T).
Reblozyl is not indicated for use as a substitute for red blood
cell transfusions in patients who require immediate correction of
anemia.
U.S. IMPORTANT SAFETY
INFORMATION
WARNINGS AND PRECAUTIONS
Thrombosis/Thromboembolism
In adult patients with beta thalassemia, thromboembolic events
(TEE) were reported in 8/223 (3.6%) of REBLOZYL-treated patients.
TEEs included deep vein thrombosis, pulmonary embolus, portal vein
thrombosis, and ischemic stroke. Patients with known risk factors
for thromboembolism (splenectomy or concomitant use of hormone
replacement therapy) may be at further increased risk of
thromboembolic conditions. Consider thromboprophylaxis in patients
at increased risk of TEE. Monitor patients for signs and symptoms
of thromboembolic events and institute treatment promptly.
Hypertension
Hypertension was reported in 10.7% (61/571) of REBLOZYL-treated
patients. Across clinical studies, the incidence of Grade 3 to 4
hypertension ranged from 1.8% to 8.6%. In patients with beta
thalassemia with normal baseline blood pressure, 13 (6.2%) patients
developed systolic blood pressure (SBP) ≥130 mm Hg and 33 (16.6%)
patients developed diastolic blood pressure (DBP) ≥80 mm Hg. In
adult patients with MDS with normal baseline blood pressure, 26
(29.9%) patients developed SBP ≥130 mm Hg and 23 (16.4%) patients
developed DBP ≥80 mm Hg. Monitor blood pressure prior to each
administration. Manage new or exacerbations of preexisting
hypertension using anti-hypertensive agents.
Extramedullary Hematopoietic Masses
In adult patients with transfusion-dependent beta thalassemia,
EMH masses were observed in 3.2% of REBLOZYL-treated patients, with
spinal cord compression symptoms due to EMH masses occurring in
1.9% of patients (BELIEVE and REBLOZYL long-term follow-up
study).
In a study of adult patients with non-transfusion-dependent beta
thalassemia, a higher incidence of EMH masses was observed in 6.3%
of REBLOZYL-treated patients vs. 2% of placebo-treated patients in
the double- blind phase of the study, with spinal cord compression
due to EMH masses occurring in 1 patient with a prior history of
EMH. REBLOZYL is not indicated for use in patients with
non-transfusion-dependent beta thalassemia.
Possible risk factors for the development of EMH masses in
patients with beta thalassemia include history of EMH masses,
splenectomy, splenomegaly, hepatomegaly, or low baseline hemoglobin
(<8.5 g/dL). Signs and symptoms may vary depending on the
anatomical location. Monitor patients with beta thalassemia at
initiation and during treatment for symptoms and signs or
complications resulting from the EMH masses and treat according to
clinical guidelines. Discontinue treatment with REBLOZYL in case of
serious complications due to EMH masses. Avoid use of REBLOZYL in
patients requiring treatment to control the growth of EMH
masses.
Embryo-Fetal Toxicity
REBLOZYL may cause fetal harm when administered to a pregnant
woman. REBLOZYL caused increased post- implantation loss, decreased
litter size, and an increased incidence of skeletal variations in
pregnant rat and rabbit studies. Advise pregnant women of the
potential risk to a fetus. Advise females of reproductive potential
to use effective contraception during treatment and for at least 3
months after the final dose.
ADVERSE REACTIONS
Beta Thalassemia
Serious adverse reactions occurred in 3.6% of patients on
REBLOZYL. Serious adverse reactions occurring in 1% of patients
included cerebrovascular accident and deep vein thrombosis. A fatal
adverse reaction occurred in 1 patient treated with REBLOZYL who
died due to an unconfirmed case of acute myeloid leukemia
(AML).
Most common adverse reactions (at least 10% for REBLOZYL and 1%
more than placebo) were headache (26% vs 24%), bone pain (20% vs
8%), arthralgia (19% vs 12%), fatigue (14% vs 13%), cough (14% vs
11%), abdominal pain (14% vs 12%), diarrhea (12% vs 10%) and
dizziness (11% vs 5%).
Myelodysplastic
Syndromes
Grade ≥3 (≥2%) adverse reactions included fatigue, hypertension,
syncope and musculoskeletal pain. A fatal adverse reaction occurred
in 5 (2.1%) patients.
The most common (≥10%) adverse reactions included fatigue,
musculoskeletal pain, dizziness, diarrhea, nausea, hypersensitivity
reactions, hypertension, headache, upper respiratory tract
infection, bronchitis, and urinary tract infection.
LACTATION
It is not known whether REBLOZYL is excreted into human milk or
absorbed systemically after ingestion by a nursing infant. REBLOZYL
was detected in milk of lactating rats. When a drug is present in
animal milk, it is likely that the drug will be present in human
milk. Because many drugs are excreted in human milk, and because of
the unknown effects of REBLOZYL in infants, a decision should be
made whether to discontinue nursing or to discontinue treatment.
Because of the potential for serious adverse reactions in the
breastfed child, breastfeeding is not recommended during treatment
and for 3 months after the last dose.
Please see full Prescribing Information for REBLOZYL.
INREBIC U.S. INDICATION
INREBIC® (fedratinib) is indicated for the treatment of adult
patients with intermediate-2 or high-risk primary or secondary
(post-polycythemia vera or post-essential thrombocythemia)
myelofibrosis (MF).
U.S. IMPORTANT SAFETY
INFORMATION
WARNING: ENCEPHALOPATHY INCLUDING WERNICKE’S Serious and
fatal encephalopathy, including Wernicke’s, has occurred in
patients treated with INREBIC. Wernicke’s encephalopathy is a
neurologic emergency. Assess thiamine levels in all patients prior
to starting INREBIC, periodically during treatment, and as
clinically indicated. Do not start INREBIC in patients with
thiamine deficiency; replete thiamine prior to treatment
initiation. If encephalopathy is suspected, immediately discontinue
INREBIC and initiate parenteral thiamine. Monitor until symptoms
resolve or improve and thiamine levels normalize.
WARNINGS AND PRECAUTIONS
Encephalopathy, including Wernicke’s: Serious and fatal
encephalopathy, including Wernicke’s encephalopathy, has occurred
in INREBIC-treated patients. Serious cases were reported in 1.3%
(8/608) of patients treated with INREBIC in clinical trials and
0.16% (1/608) of cases were fatal.
Wernicke’s encephalopathy is a neurologic emergency resulting
from thiamine (Vitamin B1) deficiency. Signs and symptoms of
Wernicke’s encephalopathy may include ataxia, mental status
changes, and ophthalmoplegia (e.g., nystagmus, diplopia). Any
change in mental status, confusion, or memory impairment should
raise concern for potential encephalopathy, including Wernicke’s,
and prompt a full evaluation including a neurologic examination,
assessment of thiamine levels, and imaging. Assess thiamine levels
in all patients prior to starting INREBIC, periodically during
treatment, and as clinically indicated. Do not start INREBIC in
patients with thiamine deficiency; replete thiamine prior to
treatment initiation. If encephalopathy is suspected, immediately
discontinue INREBIC and initiate parenteral thiamine. Monitor until
symptoms resolve or improve and thiamine levels normalize.
Anemia: New or worsening Grade 3 anemia occurred in 34%
of INREBIC-treated patients. The median time to onset of the first
Grade 3 anemia was approximately 2 months, with 75% of cases
occurring within 3 months. Mean hemoglobin levels reached nadir
after 12 to 16 weeks with partial recovery and stabilization after
16 weeks. Red blood cell transfusions were received by 51% of
INREBIC-treated patients and permanent discontinuation of INREBIC
occurred due to anemia in 1% of patients. Consider dose reduction
for patients who become red blood cell transfusion dependent.
Thrombocytopenia: New or worsening Grade ≥3
thrombocytopenia during the randomized treatment period occurred in
12% of INREBIC-treated patients. The median time to onset of the
first Grade 3 thrombocytopenia was approximately 1 month; with 75%
of cases occurring within 4 months. Platelet transfusions were
received by 3.1% of INREBIC-treated patients. Permanent
discontinuation of treatment due to thrombocytopenia and bleeding
that required clinical intervention both occurred in 2.1% of
INREBIC-treated patients. Obtain a complete blood count (CBC) at
baseline, periodically during treatment, and as clinically
indicated. For Grade 3 thrombocytopenia with active bleeding or
Grade 4 thrombocytopenia, interrupt INREBIC until resolved to less
than or equal to Grade 2 or baseline. Restart dose at 100 mg daily
below the last given dose and monitor platelets as clinically
indicated.
Gastrointestinal Toxicity: Gastrointestinal toxicities
are the most frequent adverse reactions in INREBIC-treated
patients. During the randomized treatment period, diarrhea occurred
in 66% of patients, nausea in 62% of patients, and vomiting in 39%
of patients. Grade 3 diarrhea 5% and vomiting 3.1% occurred. The
median time to onset of any grade nausea, vomiting, and diarrhea
was 1 day, with 75% of cases occurring within 2 weeks of treatment.
Consider providing appropriate prophylactic anti-emetic therapy
(e.g., 5-HT3 receptor antagonists) during INREBIC treatment. Treat
diarrhea with anti-diarrheal medications promptly at the first
onset of symptoms. Grade 3 or higher nausea, vomiting, or diarrhea
not responsive to supportive measures within 48 hours, interrupt
INREBIC until resolved to Grade 1 or less or baseline. Restart dose
at 100 mg daily below the last given dose. Monitor thiamine levels
and replete as needed.
Hepatic Toxicity: Elevations of ALT and AST (all grades)
during the randomized treatment period occurred in 43% and 40%,
respectively, with Grade 3 or 4 in 1% and 0%, respectively, of
INREBIC-treated patients. The median time to onset of any grade
transaminase elevation was approximately 1 month, with 75% of cases
occurring within 3 months. Monitor hepatic function at baseline,
periodically during treatment, and as clinically indicated. For
Grade 3 or higher ALT and/or AST elevations (greater than 5 × ULN),
interrupt INREBIC dose until resolved to Grade 1 or less or to
baseline. Restart dose at 100 mg daily below the last given dose.
If re-occurrence of a Grade 3 or higher elevation of ALT/AST,
discontinue treatment with INREBIC.
Amylase and Lipase Elevation: Grade 3 or higher amylase
2% and/or lipase 10% elevations developed in INREBIC-treated
patients. The median time to onset of any grade amylase or lipase
elevation was 15 days, with 75% of cases occurring within 1 month
of starting treatment. One patient developed pancreatitis in the
fedratinib clinical development program (n=608) and pancreatitis
resolved with treatment discontinuation. Monitor amylase and lipase
at baseline, periodically during treatment, and as clinically
indicated. For Grade 3 or higher amylase and/or lipase elevations,
interrupt INREBIC until resolved to Grade 1 or less or to baseline.
Restart dose at 100 mg daily below the last given dose.
ADVERSE REACTIONS:The most common adverse reactions for
INREBIC treated vs. placebo were diarrhea (66% vs. 16%), nausea
(62% vs. 15%), anemia (40% vs. 14%), and vomiting (39% vs. 5%).
Dosage interruptions due to an adverse reaction during the
randomized treatment period occurred in 21% of patients who
received INREBIC. Adverse reactions requiring dosage interruption
in >3% of patients who received INREBIC included diarrhea and
nausea. Dosage reductions due to an adverse reaction during the
randomized treatment period occurred in 19% of patients who
received INREBIC. Adverse reactions requiring dosage reduction in
>2% of patients who received INREBIC included anemia (6%),
diarrhea (3%), vomiting (3%), and thrombocytopenia (2%).
DRUG INTERACTIONS: Coadministration of INREBIC with a
strong CYP3A4 inhibitor increases fedratinib exposure. Increased
exposure may increase the risk of adverse reactions. Consider
alternative therapies that do not strongly inhibit CYP3A4 activity.
Alternatively, reduce the dose of INREBIC when administering with a
strong CYP3A4 inhibitor. Avoid INREBIC with strong and moderate
CYP3A4 inducers. Avoid INREBIC with dual CYP3A4 and CYP2C19
inhibitor. Coadministration of INREBIC with drugs that are CYP3A4
substrates, CYP2C19 substrates, or CYP2D6 substrates increases the
concentrations of these drugs, which may increase the risk of
adverse reactions of these drugs. Monitor for adverse reactions and
adjust the dose of drugs that are CYP3A4, CYP2C19, or CYP2D6
substrates as necessary when coadministered with INREBIC.
PREGNANCY/LACTATION: Consider the benefits and risks of
INREBIC for the mother and possible risks to the fetus when
prescribing INREBIC to a pregnant woman. Due to the potential for
serious adverse reactions in a breastfed child, advise patients not
to breastfeed during treatment with INREBIC, and for at least 1
month after the last dose.
RENAL IMPAIRMENT: Reduce INREBIC dose when administered
to patients with severe renal impairment. No modification of the
starting dose is recommended for patients with mild to moderate
renal impairment. Due to potential increase of exposure, patients
with preexisting moderate renal impairment require more intensive
safety monitoring, and if necessary, dose modifications based on
adverse reactions.
HEPATIC IMPAIRMENT: Avoid use of INREBIC in patients with
severe hepatic impairment.
Please see full Prescribing Information, including
Boxed WARNING, and Summary of Product Characteristics for
INREBIC.
ONUREG U.S. INDICATION
ONUREG® (azacitidine tablets) is approved in the U.S. for
continued treatment of adult patients with acute myeloid leukemia
who achieved first complete remission (CR) or complete remission
with incomplete blood count recovery (CRi) following intensive
induction chemotherapy and are not able to complete intensive
curative therapy.
U.S. IMPORTANT SAFETY
INFORMATION
CONTRAINDICATIONS
- ONUREG is contraindicated in patients with known severe
hypersensitivity to azacitidine or its components.
WARNINGS AND PRECAUTIONS
- Risks of Substitution with Other
Azacitidine Products: Due to substantial differences in
the pharmacokinetic parameters, the recommended dose and schedule
for ONUREG are different from those for the intravenous or
subcutaneous azacitidine products. Treatment of patients using
intravenous or subcutaneous azacitidine at the recommended dosage
of ONUREG may result in a fatal adverse reaction. Treatment with
ONUREG at the doses recommended for intravenous or subcutaneous
azacitidine may not be effective. Do not substitute ONUREG for
intravenous or subcutaneous azacitidine.
- Myelosuppression: New or
worsening Grade 3 or 4 neutropenia and thrombocytopenia occurred in
49% and 22% of patients who received ONUREG. Febrile neutropenia
occurred in 12%. A dose reduction was required for 7% and 2% of
patients due to neutropenia and thrombocytopenia. Less than 1% of
patients discontinued ONUREG due to either neutropenia or
thrombocytopenia. Monitor complete blood counts and modify the
dosage as recommended. Provide standard supportive care, including
hematopoietic growth factors, if myelosuppression occurs.
- Increased Early Mortality in Patients
with Myelodysplastic Syndromes (MDS): In AZA-MDS-003,
216 patients with red blood cell transfusion-dependent anemia and
thrombocytopenia due to MDS were randomized to ONUREG or placebo.
107 received a median of 5 cycles of ONUREG 300 mg daily for 21
days of a 28-day cycle. Enrollment was discontinued early due to a
higher incidence of early fatal and/or serious adverse reactions in
the ONUREG arm compared with placebo. The most frequent fatal
adverse reaction was sepsis. Safety and effectiveness of ONUREG for
MDS have not been established. Treatment of MDS with ONUREG is not
recommended outside of controlled trials.
- Embryo-Fetal Toxicity:
ONUREG can cause fetal harm when administered to a pregnant woman.
Azacitidine caused fetal death and anomalies in pregnant rats via a
single intraperitoneal dose less than the recommended human daily
dose of oral azacitidine on a mg/m2 basis. Advise pregnant women of
the potential risk to a fetus. Advise females of reproductive
potential to use effective contraception during treatment with
ONUREG and for at least 6 months after the last dose. Advise males
with female partners of reproductive potential to use effective
contraception during treatment with ONUREG and for at least 3
months after the last dose.
ADVERSE REACTIONS
- Serious adverse reactions occurred in 15% of patients who
received ONUREG. Serious adverse reactions in ≥2% included
pneumonia (8%) and febrile neutropenia (7%). One fatal adverse
reaction (sepsis) occurred in a patient who received ONUREG.
- Most common (≥10%) adverse reactions with ONUREG vs placebo
were nausea (65%, 24%), vomiting (60%, 10%), diarrhea (50%, 21%),
fatigue/asthenia (44%, 25%), constipation (39%, 24%), pneumonia
(27%, 17%), abdominal pain (22%, 13%), arthralgia (14%, 10%),
decreased appetite (13%, 6%), febrile neutropenia (12%, 8%),
dizziness (11%, 9%), pain in extremity (11%, 5%).
LACTATION
- There are no data regarding the presence of azacitidine in
human milk or the effects on the breastfed child or milk
production. Because of the potential for serious adverse reactions
in the breastfed child, advise women not to breastfeed during
treatment with ONUREG and for 1 week after the last dose
Please see full Prescribing Information for
ONUREG.
Cautionary Statement Regarding
Forward-Looking Statements
This press release contains “forward-looking statements” within
the meaning of the Private Securities Litigation Reform Act of 1995
regarding, among other things, the research, development and
commercialization of pharmaceutical products. All statements that
are not statements of historical facts are, or may be deemed to be,
forward-looking statements. Such forward-looking statements are
based on historical performance and current expectations and
projections about our future financial results, goals, plans and
objectives and involve inherent risks, assumptions and
uncertainties, including internal or external factors that could
delay, divert or change any of them in the next several years, that
are difficult to predict, may be beyond our control and could cause
our future financial results, goals, plans and objectives to differ
materially from those expressed in, or implied by, the statements.
These risks, assumptions, uncertainties and other factors include,
among others, that future study results will be consistent with the
results to date, that the product candidates described in this
release may not receive regulatory approval for the indications
described in this release and, if approved, whether such product
candidates for such indications will be commercially successful. No
forward-looking statement can be guaranteed. Forward-looking
statements in this press release should be evaluated together with
the many risks and uncertainties that affect Bristol Myers Squibb’s
business and market, particularly those identified in the
cautionary statement and risk factors discussion in Bristol Myers
Squibb’s Annual Report on Form 10-K for the year ended December 31,
2021, as updated by our subsequent Quarterly Reports on Form 10-Q,
Current Reports on Form 8-K and other filings with the Securities
and Exchange Commission. The forward-looking statements included in
this document are made only as of the date of this document and
except as otherwise required by applicable law, Bristol Myers
Squibb undertakes no obligation to publicly update or revise any
forward-looking statement, whether as a result of new information,
future events, changed circumstances or otherwise.
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