Pivotal trials TRANSCEND FL and TRANSCEND
NHL 001 continue to underscore the transformative potential of
Breyanzi and its clinically meaningful benefit across the broadest
array of B-cell malignancies of any CD19-directed CAR T cell
therapy
Bristol Myers Squibb (NYSE: BMY) today announced the acceptance
of two late-breaker abstracts for Breyanzi (lisocabtagene
maraleucel) studies TRANSCEND FL and TRANSCEND NHL 001 for patients
with relapsed or refractory follicular lymphoma (FL) and patients
with relapsed or refractory mantle cell lymphoma (MCL),
respectively, for presentation at the 2023 International Conference
on Malignant Lymphoma (ICML). These results follow the topline
announcement shared on May 1 of this year.
“We are dedicated to bringing new and innovative treatment
options to patients living with lymphoma and leukemia and believe
that Breyanzi provides transformative potential for patients with
heavily pre-treated relapsed or refractory follicular lymphoma or
mantle cell lymphoma,” said Anne Kerber, senior vice president,
head of Cell Therapy Development, Bristol Myers Squibb. “TRANSCEND
FL is the largest clinical trial to date evaluating CAR T cell
therapy in patients with relapsed or refractory indolent
non-Hodgkin lymphoma, including follicular lymphoma. We look
forward to sharing positive data from both this and the TRANSCEND
NHL 001 study in relapsed or refractory mantle cell lymphoma this
year at ICML.”
Late-breaker abstracts are accepted based on new, important
information that is not able to be submitted within the normal
timeline. These two studies join the list of 21 total company- and
investigator-sponsored studies and collaborations being featured at
ICML this year.
The two late-breaker studies include:
Abstract Title
Author
Session Title
Session Date/ Time (EDT)
TRANSCEND FL: Phase 2 study results of
lisocabtagene maraleucel (liso-cel) in patients (pts) with
relapsed/refractory (R/R) follicular lymphoma (FL)
Frank Morschhauser
Session 16 - Late Breaking Abstracts
Saturday, June 17, 2023 5:00 a.m. EDT
(11:00 a.m. CEST)
Lisocabtagene maraleucel (liso-cel) in
R/R MCL: primary analysis results from the MCL cohort of the
single-arm, multicenter, seamless design TRANSCEND NHL 001
study
Michael Wang
Session 16 - Late Breaking Abstracts
Saturday, June 17, 2023 4:45 a.m. EDT
(10:45 a.m. CEST)
All ICML accepted abstracts (except encore abstracts) will be
available on June 9 on the ICML website.
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
and marginal zone lymphoma. The primary outcome measure is overall
response rate. Secondary outcome measures include complete response
rate, duration of response, and progression-free survival.
About TRANSCEND NHL 001
TRANSCEND NHL 001 (NCT02631044) is an open-label, multicenter,
pivotal Phase 1, single-arm study to determine the safety,
pharmacokinetics and antitumor activity of Breyanzi in patients
with relapsed or refractory B-cell non-Hodgkin lymphoma, including
diffuse large B-cell lymphoma, high-grade B-cell lymphoma, primary
mediastinal B-cell lymphoma, follicular lymphoma grade 3B and
mantle cell lymphoma. The primary outcome measures are
treatment-related adverse events, dose-limiting toxicities and
overall response rate. Secondary outcome measures include complete
response rate, duration of response and progression-free
survival.
About FL
Follicular lymphoma (FL) is the second most common, slow-growing
form of non-Hodgkin lymphoma (NHL), accounting for 20-30% of all
NHL cases. Most patients with FL are over 50 years of age when they
are diagnosed. 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 MCL
Mantle cell lymphoma (MCL) is an aggressive, rare form of
non-Hodgkin lymphoma (NHL), representing roughly 3% of all NHL
cases. MCL originates from cells in the “mantle zone” of the lymph
node. MCL occurs more frequently in older adults with an average
age at diagnosis in the mid-60s, and is more often found in males
than in females. In MCL, relapse after initial treatment is common,
and for most, the disease eventually progresses or returns.
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 by the U.S. Food and Drug Administration (FDA)
for the treatment of adult patients with LBCL, including diffuse
large B-cell lymphoma (DLBCL) not otherwise specified (including
DLBCL arising from indolent lymphoma), high-grade B-cell lymphoma,
primary mediastinal LBCL, 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 transplant due to comorbidities or age, or
relapsed or refractory disease after two or more lines of systemic
therapy. Breyanzi is not indicated for the treatment of patients
with primary central nervous system lymphoma.
Please see the Important Safety Information section below,
including Boxed WARNINGS for Breyanzi regarding cytokine release
syndrome and neurotoxicity.
Breyanzi is also approved in Japan and Europe for the
second-line treatment of relapsed or refractory LBCL, and in Japan,
Europe, Switzerland, 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 earlier lines of treatment for patients with relapsed or
refractory LBCL and other types of lymphoma and leukemia. For more
information, visit clinicaltrials.gov.
U.S. Important Safety
Information
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.
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 (CRS)
Cytokine release syndrome (CRS), including fatal or
life-threatening reactions, occurred following treatment with
BREYANZI. Among patients receiving BREYANZI for LBCL (N=418), CRS
occurred in 46% (190/418), 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, and hemoglobin 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 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.
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,
that future study results may not be consistent with the results to
date, that Breyanzi (lisocabtagene maraleucel) may not receive
regulatory approval for the additional indication described in this
release in the currently anticipated timeline or at all, that any
marketing approvals, if granted, may have significant limitations
on their use, and, if approved, whether such product candidate for
such additional indication described in this release 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, 2022, 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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