95.7% of patients responded to Breyanzi in
the TRANSCEND FL trial
Breyanzi provided sustained clinical benefit
with median duration of response not reached and the majority
(77.1%) of responders in ongoing response at 18 months
Breyanzi is a personalized therapy with a
differentiated profile, offering durable responses and a consistent
safety profile across trials
Bristol Myers Squibb (NYSE: BMY) today announced the U.S. Food
and Drug Administration (FDA) has granted accelerated approval for
Breyanzi® (lisocabtagene maraleucel; liso-cel), a CD19-directed
chimeric antigen receptor (CAR) T cell therapy, for the treatment
of adult patients with relapsed or refractory follicular lymphoma
(FL) who have received two or more prior lines of systemic therapy.
This indication is approved under accelerated approval based on
response rate and duration of response. Continued approval for this
indication may be contingent upon verification and description of
clinical benefit in confirmatory trial(s). Breyanzi is also now
included in the National Comprehensive Cancer Network (NCCN®)
Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for
B-cell Lymphomas as a Category 2A recommendation for third-line and
subsequent therapy for relapsed or refractory FL.*
This press release features multimedia. View
the full release here:
https://www.businesswire.com/news/home/20240515772899/en/
Product image for download (Photo:
Bristol Myers Squibb)
In relapsed or refractory FL, Breyanzi is delivered as a
one-time infusion** with a single dose containing 90 to 110 x 106
CAR-positive viable T cells. Please see the Important Safety
Information section below, including Boxed WARNINGS for
Breyanzi regarding Cytokine Release Syndrome (CRS), Neurologic
Toxicities, and Secondary Hematological Malignancies.
“Breyanzi is a cornerstone of our cell therapy portfolio,
providing a differentiated profile across a wide array of B-cell
malignancies,” said Bryan Campbell, senior vice president, Head of
Commercial, Cell Therapy, Bristol Myers Squibb. “Today’s approval
of Breyanzi for relapsed or refractory FL provides an option with
potential for lasting remission in a one-time infusion and a safety
profile that allows for administration and monitoring in both the
inpatient and outpatient setting in an increasing number of
certified treatment centers in the U.S.”
Historically, FL has been considered an incurable disease, and
patients frequently relapse following front-line therapy, with
prognosis worsening after each subsequent relapse. Despite advances
in treatment, there remains an unmet need for additional options
that offer treatment-free intervals with durable, complete
responses.
The Phase 2 TRANSCEND FL study included the largest primary
analysis set of patients with relapsed or refractory FL of a
clinical trial evaluating a CAR T cell therapy in this patient
population. Based on the U.S. Prescribing Information (USPI), in
patients treated with Breyanzi in the third-line plus setting and
included in the primary efficacy analysis set (n=94), the overall
response rate (ORR) was 95.7% (95% CI: 89.5-98.8). ORR was defined
as the percentage of patients achieving a partial or complete
response per Lugano criteria as assessed by an Independent Review
Committee (IRC). The complete response (CR) rate was 73.4% (95% CI:
63.3-82.0) and required a negative bone marrow biopsy for
confirmation. Responses were rapid and durable with a median time
to response of one month (range: 0.6-3.3) and median duration of
response (DOR) not reached (95% CI: 18.04-NR), with 80.9% of
responders remaining in response at 12 months, and 77.1% of
responders remaining in response at 18 months. Results from the
primary analysis of TRANSCEND FL presented at the 2023
International Conference on Malignant Lymphoma showed an ORR of 97%
(95% CI: 91.6-99.4; one-sided p<0.0001) in efficacy evaluable
patients (n=101), with 94% of patients achieving a CR (95% CI:
87.5-97.8; one-sided p<0.0001).
“In the treatment of relapsed or refractory follicular lymphoma,
patients often cycle through treatments with typically shorter
responses with each new line of therapy. Those who have experienced
early disease progression have notably poor prognosis,” said M. Lia
Palomba, M.D., TRANSCEND investigator and lymphoma and cell therapy
specialist, Memorial Sloan Kettering Cancer Center. “The FDA
approval of liso-cel for patients with relapsed or refractory FL is
an important advancement in addressing an ongoing unmet need in the
FL treatment paradigm, providing patients a new option that has
shown remarkably high response rates and an established safety
profile.”
Breyanzi has exhibited a consistent safety profile and across
clinical trials, any grade cytokine release syndrome (CRS) occurred
in 53% of patients, including Grade >3 CRS in 4% of patients. The median time to
onset was 5 days (range: 1 to 63 days). Any grade neurologic events
(NEs) occurred in 31% of patients, with Grade >3 NEs occurring in 10% of patients. The median
time to onset of NEs was 8 days (range: 1 to 63 days). The safety
profile of Breyanzi allows for the option of outpatient treatment
and management of patients. Patients in the TRANSCEND FL study were
treated in the inpatient and outpatient setting.
“The lymphoma community has felt an urgent need for advancements
in the treatment of relapsed or refractory follicular lymphoma,”
said Meghan Gutierrez, chief executive officer, Lymphoma Research
Foundation. “The approval of Breyanzi offers patients a new and
meaningful treatment option that provides hope for lasting
remission, and we are grateful to those who have contributed to
this exciting milestone for patients.”
Bristol Myers Squibb offers various programs and resources to
address the needs of patients and caregivers, and provides support
that allows for access to therapies, including Breyanzi. Bristol
Myers Squibb also supports the patient and physician treatment
experience by providing Cell Therapy 360, a digital service
platform, which optimizes access to relevant information,
manufacturing updates, and patient and caregiver support.
*NCCN makes no warranties of any kind whatsoever regarding their
content, use or application and disclaims any responsibility for
their application or use in any way. **Treatment process includes
leukapheresis, manufacturing, administration, and adverse event
monitoring.
About TRANSCEND FL TRANSCEND
FL (NCT04245839) is an open-label, global, multicenter, Phase 2,
single-arm study to determine the efficacy and safety of Breyanzi
in patients with relapsed or refractory indolent B-cell non-Hodgkin
lymphoma, including follicular lymphoma. The primary outcome
measure is overall response rate, including best overall response
of complete response or partial response as determined by an
Independent Review Committee. Secondary outcome measures include
complete response rate, duration of response, progression-free
survival, and safety.
About FL Follicular lymphoma
(FL) is the second most common form of non-Hodgkin lymphoma (NHL)
and the most common subtype of indolent NHL, accounting for 20 to
30 percent of all NHL cases. The average age of diagnosis for FL is
65 years of age. FL develops when white blood cells cluster
together to form lumps in a person’s lymph nodes or organs. It is
characterized by periods of remission and relapse, and the disease
becomes more difficult to treat after relapse or disease
progression.
About Breyanzi Breyanzi is a
CD19-directed CAR T cell therapy with a 4-1BB costimulatory domain,
which enhances the expansion and persistence of the CAR T cells.
Breyanzi is made from a patient’s own T cells, which are collected
and genetically reengineered to become CAR T cells that are then
delivered via infusion as a one-time treatment.
Breyanzi is approved in the U.S. for the treatment of relapsed
or refractory large B-cell lymphoma (LBCL) after at least one prior
line of therapy and received accelerated approval for the treatment
of relapsed or refractory chronic lymphocytic leukemia or small
lymphocytic lymphoma after at least two prior lines of therapy.
Breyanzi is also approved in Japan, the European Union (EU), and
Switzerland for the second-line treatment or relapsed or refractory
LBCL, and in Japan, the European Union, Switzerland, the UK and
Canada 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 other types of lymphoma. For more
information, visit clinicaltrials.gov.
Indication BREYANZI is a
CD19-directed genetically modified autologous T cell immunotherapy
indicated for the treatment of:
- adult patients with large B-cell lymphoma (LBCL), 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, who have:
- refractory disease to first-line chemoimmunotherapy or relapse
within 12 months of first-line chemoimmunotherapy; or
- refractory disease to first-line chemoimmunotherapy or relapse
after first-line chemoimmunotherapy and are not eligible for
hematopoietic stem cell transplantation (HSCT) due to comorbidities
or age; or
- relapsed or refractory disease after two or more lines of
systemic therapy.
Limitations of Use: BREYANZI is not
indicated for the treatment of patients with primary central
nervous system lymphoma.
- Adult patients with relapsed or refractory chronic lymphocytic
leukemia (CLL) or small lymphocytic lymphoma (SLL) who have
received at least 2 prior lines of therapy, including a Bruton
tyrosine kinase (BTK) inhibitor and a B-cell lymphoma 2 (BCL-2)
inhibitor. This indication is approved under accelerated approval
based on response rate and duration of response. Continued approval
for this indication may be contingent upon verification and
description of clinical benefit in confirmatory trial(s).
- Adult patients with relapsed or refractory follicular lymphoma
(FL) who have received 2 or more prior lines of systemic therapy.
This indication is approved under accelerated approval based on
response rate and duration of response. Continued approval for this
indication may be contingent upon verification and description of
clinical benefit in confirmatory trial(s).
Important Safety
Information
BOXED WARNING: CYTOKINE RELEASE SYNDROME, NEUROLOGIC
TOXICITIES, AND SECONDARY HEMATOLOGICAL MALIGNANCIES
- 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.
- T cell malignancies have occurred following treatment of
hematologic malignancies with BCMA- and CD19-directed genetically
modified autologous T cell immunotherapies, including
BREYANZI.
- BREYANZI is available only through a restricted program
under a Risk Evaluation and Mitigation Strategy (REMS) called the
BREYANZI REMS.
Cytokine Release Syndrome (CRS) Cytokine release syndrome
(CRS), including fatal or life-threatening reactions, occurred
following treatment with BREYANZI. In clinical trials of BREYANZI
which enrolled a total of 614 patients with non-Hodgkin lymphoma
(NHL), CRS occurred in 53% of patients, including Grade 3 or higher
CRS in 4% of patients. The median time to onset was 5 days (range:
1 to 63 days). CRS resolved in 98% of patients with median duration
of 5 days (range: 1 to 37 days). The most common manifestations of
CRS (>10%) were fever, hypotension,
tachycardia, chills, hypoxia and headache.
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.
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 clinical trials of BREYANZI, CAR T cell-associated neurologic
toxicities occurred in 31% of patients, including > Grade 3 cases in 10% of patients. The median
time to onset of neurotoxicity was 8 days (range: 1 to 63 days).
Neurologic toxicities resolved in 87% of patients with a median
duration of 8 days (range: 1 to 119 days). Of patients developing
neurotoxicity, 81% also developed CRS.
The most common neurologic toxicities (≥ 5%) included
encephalopathy, tremor, aphasia, headache, dizziness, and
delirium.
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.
Further information is available at www.BreyanziREMS.com, or
contact Bristol Myers Squibb at 1-866-340-7332.
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 clinical trials of BREYANZI, infections
of any grade occurred in 33% of patients, 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 in 4%, viral infections in 2%, and fungal infections in
0.7% of patients. One patient who received four prior lines of
therapy developed a fatal case of John Cunningham (JC) virus
progressive multifocal leukoencephalopathy four months after
treatment with BREYANZI.
Febrile neutropenia developed after BREYANZI infusion in 8% of
patients. 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 clinical trials of BREYANZI, 26 of 29 patients with 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. In clinical trials of BREYANZI, Grade 3 or
higher cytopenias persisted at Day 29 following BREYANZI infusion
in 34% of patients, and included thrombocytopenia in 24%,
neutropenia in 22%, and anemia in 7% of patients. 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 clinical trials of BREYANZI,
hypogammaglobulinemia was reported as an adverse reaction in 10% of
patients. Hypogammaglobulinemia, either as an adverse reaction or
laboratory IgG level below 500 mg/dL after infusion, was reported
in 29% 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. T cell malignancies have occurred
following treatment of hematologic malignancies with BCMA- and
CD19-directed genetically modified autologous T cell
immunotherapies, including BREYANZI. Mature T cell malignancies,
including CAR-positive tumors, may present as soon as weeks
following infusion, and may include fatal outcomes. 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.
Immune Effector Cell-Associated Hemophagocytic
Lymphohistiocytosis-Like Syndrome (IEC-HS) Immune Effector
Cell-Associated Hemophagocytic Lymphohistiocytosis (IEC-HS),
including fatal or life-threatening reactions, occurred following
treatment with BREYANZI. Three of 89 (3%) safety evaluable patients
with R/R CLL/SLL developed IEC-HS. Time to onset of IEC-HS ranged
from 7 to 18 days. Two of the 3 patients developed IEC-HS in the
setting of ongoing CRS and 1 in the setting of ongoing
neurotoxicity. IEC-HS was fatal in 2 of 3 patients. One patient had
fatal IEC-HS and one had ongoing IEC-HS at time of death. IEC-HS is
a life-threatening condition with a high mortality rate if not
recognized and treated early. Treatment of IEC-HS should be
administered per current practice guidelines.
Adverse Reactions The most common adverse reactions
(incidence ≥ 30%) in:
- LBCL are fever, cytokine release syndrome, fatigue,
musculoskeletal pain, and nausea. The most common Grade 3-4
laboratory abnormalities include lymphocyte count decrease,
neutrophil count decrease, platelet count decrease, and hemoglobin
decrease.
- CLL/SLL are cytokine release syndrome, encephalopathy, fatigue,
musculoskeletal pain, nausea, edema, and diarrhea. The most common
Grade 3-4 laboratory abnormalities include neutrophil count
decrease, white blood cell decrease, hemoglobin decrease, platelet
count decrease, and lymphocyte count decrease.
- FL are cytokine release syndrome. The most common Grade 3-4
laboratory abnormalities include lymphocyte count decreased,
neutrophil count decreased, and white blood cell decrease.
Please see full Prescribing Information,
including Boxed WARNINGS and Medication
Guide.
Bristol Myers Squibb: Creating a Better
Future for People with Cancer 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
understanding of causal human biology, cutting-edge capabilities
and differentiated research platforms uniquely position the company
to approach 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. As a
leader in cancer care, Bristol Myers Squibb is working to empower
all people with cancer to have a better future.
Learn more about the science behind cell therapy and ongoing
research at Bristol Myers Squibb here.
About Bristol Myers Squibb
Bristol Myers Squibb is a global biopharmaceutical company whose
mission is to discover, develop and deliver innovative medicines
that help patients prevail over serious diseases. For more
information about Bristol Myers Squibb, visit us at BMS.com or
follow us on LinkedIn, Twitter, YouTube, Facebook and
Instagram.
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 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, whether Breyanzi
(lisocabtagene maraleucel) for the additional indication described
in this release will be commercially successful, any marketing
approvals, if granted, may have significant limitations on their
use, and that continued approval of Breyanzi for such additional
indication described in this release may be contingent upon
verification and description of clinical benefit in confirmatory
trials. 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, 2023, 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.
corporatefinancial-news
View source
version on businesswire.com: https://www.businesswire.com/news/home/20240515772899/en/
Bristol Myers Squibb Media Inquiries:
media@bms.com
Investors: investor.relations@bms.com
Bristol Myers Squibb (NYSE:BMY)
Historical Stock Chart
From Sep 2024 to Oct 2024
Bristol Myers Squibb (NYSE:BMY)
Historical Stock Chart
From Oct 2023 to Oct 2024
