Bristol Myers Squibb (NYSE: BMY) today announced topline results
from TRANSCEND CLL 004, a Phase 1/2, open-label, single-arm,
multicenter study evaluating Breyanzi (lisocabtagene maraleucel) in
adults with relapsed or refractory (R/R) chronic lymphocytic
leukemia (CLL) or small lymphocytic lymphoma (SLL). Results from
TRANSCEND CLL 004 showed the study met the primary endpoint of
complete response rate compared to historical control in the
prespecified subset of patients with R/R CLL that was refractory to
a BTK inhibitor and pretreated with a BCL-2 inhibitor. No new
safety signals were reported for Breyanzi in this study.
“CLL is an incurable disease with complex biology and immune
dysregulation that has made the development of T cell-based
therapies that provide deep remission very challenging,” said Anne
Kerber, senior vice president, head of Cell Therapy Development,
Bristol Myers Squibb. “In a population that has limited options,
the TRANSCEND CLL 004 study represents the first multicenter trial
evaluating a CAR T cell therapy in heavily pre-treated patients
with relapsed or refractory CLL or SLL, with results showing the
potential of Breyanzi as a personalized one-time treatment approach
for patients with this difficult-to-treat disease.”
Bristol Myers Squibb will complete a full evaluation of the
TRANSCEND CLL 004 data and work with investigators to present
detailed results at an upcoming medical meeting, as well as discuss
these results with health authorities. Bristol Myers Squibb thanks
the patients and investigators who are participating in the
TRANSCEND CLL 004 clinical trial.
About TRANSCEND CLL 004
TRANSCEND CLL 004 (NCT03331198) is a Phase 1/2 open-label,
single-arm, multicenter study evaluating Breyanzi in patients with
relapsed or refractory chronic lymphocytic leukemia or small
lymphocytic lymphoma. The Phase 1 dose escalation portion of the
study assessed the safety and recommended dose for the subsequent
Phase 2 expansion cohort. The Phase 2 portion of the study is
evaluating Breyanzi at the recommended dose from the Phase 1
monotherapy arm. The primary endpoint of the Phase 2 portion of the
study was complete response rate, including complete remission with
incomplete bone marrow recovery, based on independent review
committee according to the International Workshop on Chronic
Lymphocytic Leukemia (iwCLL) 2018 guidelines.
About CLL and SLL
Chronic lymphocytic leukemia (CLL) is one of the most common
types of leukemia in adults. In CLL, too many blood stem cells in
the bone marrow become abnormal lymphocytes, and these abnormal
cells have difficulty fighting infections. As the number of
abnormal cells grows, there is less room for healthy white blood
cells, red blood cells and platelets. Small lymphocytic lymphoma
(SLL) also affects the lymphocytes, with cancer cells found mostly
in the lymph nodes. While there are several treatments available
for CLL and SLL, there is a need for additional effective therapies
as there is no standard of care for relapsed or refractory CLL or
SLL after prior therapy with targeted agents. Patients with
relapsed or refractory disease have limited treatment options and
generally experience shorter periods of response with each
subsequent treatment.
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 approved by the U.S. Food and Drug
Administration (FDA) 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
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 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 and leukemias. 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 (CRS)
CRS, including fatal or life-threatening reactions, occurred
following treatment with BREYANZI. CRS occurred in 46% (122/268) of
patients receiving BREYANZI, including ≥ Grade 3 (Lee grading
system) CRS in 4% (11/268) 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 119 of 122
patients (98%) with a median duration of 5 days (range: 1 to 17
days). Median duration of CRS was 5 days (range 1 to 30 days) in
all patients, including those who died or had CRS ongoing at time
of death.
Among patients with CRS, the most common manifestations of CRS
include fever (93%), hypotension (49%), tachycardia (39%), chills
(28%), and hypoxia (21%). 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. Sixty-one of 268 (23%) patients received
tocilizumab and/or a corticosteroid for CRS after infusion of
BREYANZI. Twenty-seven (10%) patients received tocilizumab only, 25
(9%) received tocilizumab and a corticosteroid, and 9 (3%) received
corticosteroids only.
Neurologic Toxicities
Neurologic toxicities that were fatal or life-threatening,
occurred following treatment with BREYANZI. CAR T cell-associated
neurologic toxicities occurred in 35% (95/268) of patients
receiving BREYANZI, including ≥ Grade 3 in 12% (31/268) of
patients. Three patients had fatal neurologic toxicity and 7 had
ongoing neurologic toxicity at time of death. The median time to
onset of the first event was 8 days (range: 1 to 46 days). The
onset of all neurologic events occurred within the first 8 weeks
following BREYANZI infusion. Neurologic toxicities resolved in 81
of 95 patients (85%) with a median duration of 12 days (range: 1 to
87 days). Three of four patients with ongoing neurologic toxicity
at data cutoff had tremor and one subject had encephalopathy.
Median duration of neurologic toxicity was 15 days (range: 1 to 785
days) in all patients, including those with ongoing neurologic
events at the time of death or at data cutoff.
Seventy-eight (78) of 95 (82%) patients with neurologic toxicity
experienced CRS. Neurologic toxicity overlapped with CRS in 57
patients. The onset of neurologic toxicity was after onset of CRS
in 30 patients, before CRS onset in 13 patients, same day as CRS
onset in 7 patients, and same day as CRS resolution in 7 patients.
Neurologic toxicity resolved in three patients before the onset of
CRS. Eighteen patients experienced neurologic toxicity after
resolution of CRS.
The most common neurologic toxicities included encephalopathy
(24%), tremor (14%), aphasia (9%), delirium (7%), headache (7%),
dizziness (6%), and ataxia (6%). Serious events including cerebral
edema and seizures occurred with BREYANZI. Fatal and serious cases
of leukoencephalopathy, some attributable to fludarabine, have
occurred in patients treated with BREYANZI.
CRS and Neurologic Toxicities Monitoring
Monitor patients daily at a certified healthcare facility during
the first week following infusion, for signs and symptoms of CRS
and neurologic toxicities. Monitor patients for signs and symptoms
of CRS and neurologic toxicities for at least 4 weeks after
infusion; evaluate and treat promptly. Counsel patients to seek
immediate medical attention should signs or symptoms of CRS or
neurologic toxicity occur at any time. At the first sign of CRS,
institute treatment with supportive care, tocilizumab or
tocilizumab and corticosteroids as indicated.
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.
Infections (all grades) occurred in 45% (121/268) of patients.
Grade 3 or higher infections occurred in 19% of patients. Grade 3
or higher infections with an unspecified pathogen occurred in 16%
of patients, bacterial infections occurred in 5%, and viral and
fungal infections occurred in 1.5% and 0.4% of patients,
respectively. Monitor patients for signs and symptoms of infection
before and after BREYANZI administration and treat appropriately.
Administer prophylactic antimicrobials according to standard
institutional guidelines.
Febrile neutropenia has been observed in 9% (24/268) of patients
after BREYANZI 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.
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. Ten of the 11 patients in the TRANSCEND study with a prior
history of HBV were treated with concurrent antiviral suppressive
therapy to prevent HBV reactivation during and after treatment with
BREYANZI. Perform screening for HBV, HCV, and HIV in accordance
with clinical guidelines before collection of cells for
manufacturing.
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 31% (84/268) of patients, and included thrombocytopenia
(26%), neutropenia (14%), and anemia (3%). Monitor complete blood
counts prior to and after BREYANZI administration.
Hypogammaglobulinemia
B-cell aplasia and hypogammaglobulinemia can occur in patients
receiving treatment with BREYANZI. The adverse event of
hypogammaglobulinemia was reported as an adverse reaction in 14%
(37/268) of patients; laboratory IgG levels fell below 500 mg/dL
after infusion in 21% (56/268) of patients. Hypogammaglobulinemia,
either as an adverse reaction or laboratory IgG level below 500
mg/dL after infusion, was reported in 32% (85/268) 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 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, during this initial period.
Adverse Reactions
Serious adverse reactions occurred in 46% of patients. The most
common nonlaboratory, serious adverse reactions (> 2%) were CRS,
encephalopathy, sepsis, febrile neutropenia, aphasia, pneumonia,
fever, hypotension, dizziness, and delirium. Fatal adverse
reactions occurred in 4% of patients.
The most common nonlaboratory adverse reactions of any grade (≥
20%) were fatigue, CRS, musculoskeletal pain, nausea, headache,
encephalopathy, infections (pathogen unspecified), decreased
appetite, diarrhea, hypotension, tachycardia, dizziness, cough,
constipation, abdominal pain, vomiting, and edema.
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, 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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