Study of the first and only subcutaneous
quadruplet regimen demonstrates 60.9 percent improvement in
minimal residual disease (MRD)-negativity and 43 percent
reduction in the risk of progression or death
Phase 3 CEPHEUS study results presented in
late-breaking oral presentation at the International Myeloma
Society (IMS) Annual Meeting
RIO DE
JANEIRO, Sept. 27, 2024 /PRNewswire/
-- Johnson & Johnson (NYSE:JNJ) announced today results
from the Phase 3 CEPHEUS study demonstrating a significant clinical
improvement with DARZALEX FASPRO® (daratumumab
and hyaluronidase-fihj) in combination with bortezomib,
lenalidomide and dexamethasone (D-VRd) in the treatment of patients
with newly diagnosed multiple myeloma (NDMM) who are transplant
ineligible (TIE) or for whom transplant was not planned as initial
therapy (transplant deferred). The data showing significant
improvement in minimal residual disease (MRD) negativity rate,
progression-free survival (PFS) and complete response (CR) or
better rate, were featured as a late-breaking oral presentation at
the 2024 International Myeloma Society (IMS) Annual Meeting
(Abstract #OA — 63).
CEPHEUS is an ongoing, multicenter, randomized, open-label,
Phase 3 study evaluating the efficacy and safety of D-VRd compared
to bortezomib, lenalidomide and dexamethasone (VRd) for NDMM
patients for whom transplant was not planned as initial therapy
(TIE or deferred). Results show that treatment with D-VRd
resulted in deeper responses, including MRD-negativity, compared
with VRd. At a median follow-up of 58.7 months, the primary
endpoint was met, with overall MRD-negativity rate at a sensitivity
of 10-5 (no cancer cells detected within 100,000 bone
marrow cells) of 60.9 percent for patients receiving D-VRd and 39.4
percent for VRd (OR [odds ratio], 2.37; 95% confidence interval
[CI], 1.58-3.55; P<0.0001). The proportion of patients
achieving sustained MRD-negativity of ≥ 12 months almost
doubled with D-VRd vs VRd (48.7 percent vs 26.3 percent;
P<0.0001). The study also demonstrated that D-VRd
significantly reduced the risk of progression or death by 43
percent (HR [hazard ratio], 0.57; 95% CI, 0.41-0.79;
P<0.0005) vs VRd. The median PFS was not reached for
D-VRd vs 52.6 months for VRd.1
"The CEPHEUS study results show that 60 percent of patients
achieved MRD negativity, which is clinically important for
physicians treating patients with multiple myeloma and, in general,
a strong predictor of improved long-term outcomes, including
progression free survival and overall survival," said Saad Z. Usmani, M.D., F.A.C.P., Chief, Myeloma
Service, Memorial Sloan Kettering Cancer Center and study
investigator.* "The subcutaneous daratumumab-based quadruplet
regimen has compelling efficacy characterized by deep, durable
responses and reduced risk of disease progression in the frontline
population of patients not undergoing transplant, supporting the
potential of this quadruplet to become a new regimen in this
treatment setting."
The DARZALEX FASPRO®-based quadruplet regimen,
compared to VRd, also significantly increased the depth of response
with higher rates of CR or better. The CR or better rate was 81.2
percent with D-VRd vs 61.6 percent with VRd (P<0.0001).
Overall survival data are not yet mature. The overall safety
profile of D-VRd was consistent with the known safety profiles for
DARZALEX FASPRO® and VRd. The most common (>10
percent) Grade 3/4 hematologic and non-hematologic adverse events
with D-VRd vs VRd were neutropenia (44.2 percent vs 29.7 percent),
thrombocytopenia (28.4 percent vs 20.0 percent), anemia (13.2
percent vs 11.8 percent), peripheral neuropathies (8.1 percent vs
8.2 percent), diarrhea (12.2 percent vs 9.2 percent), and COVID-19
(11.2 percent vs 4.6 percent).1
"Data from PERSEUS and now CEPHEUS add to the body of evidence
illustrating how the DARZALEX FASPRO®-based
quadruplet regimen has the potential to be a foundational frontline
therapy across all patient types during first-line treatment,
regardless of transplant eligibility status," said Robin Carson, M.D., Global Head, Oncology,
Innovative Medicine, Johnson & Johnson. "We look forward to
continuing to advance this potential new quadruplet therapy and
deliver on our commitment to transforming outcomes for people with
multiple myeloma."
About the CEPHEUS Study
CEPHEUS (NCT03652064) is an
ongoing, multicenter, randomized, open-label, Phase 3 study
comparing the efficacy and safety of D-VRd vs VRd in patients with
newly diagnosed multiple myeloma for whom autologous stem cell
transplant (ASCT) is not planned as initial therapy. The primary
endpoint is minimal residual disease (MRD)-negativity rate at a
10-5 sensitivity threshold. Key secondary endpoints
include overall complete response (CR) or better rate,
progression-free survival (PFS), and sustained MRD-negative rate at
1 year. The trial has enrolled 396 patients in 13 countries.
About the PERSEUS Study
The PERSEUS study
(NCT03710603) is being conducted in collaboration with the European
Myeloma Network as the sponsor. PERSEUS is an ongoing,
randomized, open-label, Phase 3 study comparing the efficacy and
safety of D-VRd during induction and consolidation versus VRd
during induction and consolidation in patients with NDMM eligible
for autologous stem cell transplant (ASCT). Following
consolidation, patients received an investigational treatment
regimen for maintenance that included DARZALEX
FASPRO® in combination with lenalidomide or
lenalidomide alone. The trial was not designed to isolate the
effect of DARZALEX FASPRO® in the maintenance
phase of treatment. The efficacy of DARZALEX
FASPRO® in combination with lenalidomide for
maintenance has not been established. The primary endpoint is PFS,
and secondary endpoints include overall CR or better rate, and
overall MRD-negativity (in patients with CR or better). The median
age is 61.0 (range, 32-70) years for patients in the D-VRd arm and
59.0 (range, 31-70) years for patients in the VRd arm. The study is
being conducted in 14 countries in Europe and Australia.
About Multiple Myeloma
Multiple myeloma is a blood
cancer that affects a type of white blood cell called plasma cells,
which are found in the bone marrow.2 In multiple
myeloma, these malignant plasma cells proliferate and replace
normal cells in the bone marrow.3 Multiple myeloma is
the second most common blood cancer worldwide and remains an
incurable disease.4 In 2024, it is estimated that more
than 35,000 people will be diagnosed with multiple myeloma in the
U.S. and more than 12,000 will die from the disease.5
People with multiple myeloma have a 5-year survival rate of 59.8
percent.5 While some people diagnosed with multiple
myeloma initially have no symptoms, most patients are diagnosed due
to symptoms that can include bone fracture or pain, low red blood
cell counts, tiredness, high calcium levels, kidney problems or
infections.6,7
About DARZALEX FASPRO®
DARZALEX
FASPRO® (daratumumab and hyaluronidase-fihj)
received U.S. FDA approval in May
2020 and is approved for nine indications in multiple
myeloma, four of which are for frontline treatment in newly
diagnosed patients who are transplant eligible or
ineligible.1 It is the only subcutaneous CD38-directed
antibody approved to treat patients with multiple myeloma. DARZALEX
FASPRO® is co-formulated with recombinant human
hyaluronidase PH20 (rHuPH20), Halozyme's ENHANZE® drug
delivery technology.
In August 2012, Janssen Biotech,
Inc. and Genmab A/S entered a worldwide agreement, which granted
Janssen an exclusive license to develop, manufacture and
commercialize daratumumab.
For more information, visit https://www.darzalexhcp.com.
DARZALEX FASPRO® INDICATIONS AND IMPORTANT
SAFETY INFORMATION
INDICATIONS
DARZALEX FASPRO® (daratumumab and
hyaluronidase-fihj) is indicated for the treatment of adult
patients with multiple myeloma:
- In combination with bortezomib, lenalidomide, and dexamethasone
for induction and consolidation in newly diagnosed patients who are
eligible for autologous stem cell transplant
- In combination with bortezomib, melphalan, and prednisone in
newly diagnosed patients who are ineligible for autologous stem
cell transplant
- In combination with lenalidomide and dexamethasone in newly
diagnosed patients who are ineligible for autologous stem cell
transplant and in patients with relapsed or refractory multiple
myeloma who have received at least one prior therapy
- In combination with bortezomib, thalidomide, and dexamethasone
in newly diagnosed patients who are eligible for autologous stem
cell transplant
- In combination with pomalidomide and dexamethasone in patients
who have received at least one prior line of therapy including
lenalidomide and a proteasome inhibitor (PI)
- In combination with carfilzomib and dexamethasone in patients
with relapsed or refractory multiple myeloma who have received one
to three prior lines of therapy
- In combination with bortezomib and dexamethasone in patients
who have received at least one prior therapy
- As monotherapy in patients who have received at least three
prior lines of therapy including a PI and an immunomodulatory agent
or who are double refractory to a PI and an immunomodulatory
agent
IMPORTANT SAFETY INFORMATION
CONTRAINDICATIONS
DARZALEX FASPRO®
is contraindicated in patients with a history of severe
hypersensitivity to daratumumab, hyaluronidase, or any of the
components of the formulation.
WARNINGS AND PRECAUTIONS
Hypersensitivity and Other Administration
Reactions
Both systemic administration-related reactions,
including severe or life-threatening reactions, and local
injection-site reactions can occur
with DARZALEX FASPRO®. Fatal reactions have been
reported with daratumumab-containing products, including DARZALEX
FASPRO®.
Systemic Reactions
In a pooled safety population of
1249 patients with multiple myeloma (N=1056) or light chain
(AL) amyloidosis (N=193) who received DARZALEX
FASPRO® as monotherapy or in combination, 7% of
patients experienced a systemic administration-related reaction
(Grade 2: 3.2%, Grade 3: 0.7%, Grade 4: 0.1%). Systemic
administration-related reactions occurred in 7% of patients with
the first injection, 0.2% with the second injection, and
cumulatively 1% with subsequent injections. The median time to
onset was 2.9 hours (range: 5 minutes to 3.5 days). Of
the 165 systemic administration-related reactions that
occurred in 93 patients, 144 (87%) occurred on the day of
DARZALEX FASPRO® administration. Delayed systemic
administration-related reactions have occurred in 1% of the
patients.
Severe reactions included hypoxia, dyspnea, hypertension,
tachycardia, and ocular adverse reactions, including choroidal
effusion, acute myopia, and acute angle closure glaucoma. Other
signs and symptoms of systemic administration-related reactions may
include respiratory symptoms, such as bronchospasm, nasal
congestion, cough, throat irritation, allergic rhinitis, and
wheezing, as well as anaphylactic reaction, pyrexia, chest pain,
pruritus, chills, vomiting, nausea, hypotension, and blurred
vision.
Pre-medicate patients with histamine-1 receptor antagonist,
acetaminophen, and corticosteroids. Monitor patients for systemic
administration-related reactions, especially following the first
and second injections. For anaphylactic reaction or
life-threatening (Grade 4) administration-related reactions,
immediately and permanently discontinue DARZALEX
FASPRO®. Consider administering corticosteroids
and other medications after the administration of DARZALEX
FASPRO® depending on dosing regimen and
medical history to minimize the risk of delayed (defined as
occurring the day after administration) systemic
administration-related reactions.
Ocular adverse reactions, including acute myopia and narrowing
of the anterior chamber angle due to ciliochoroidal effusions with
potential for increased intraocular pressure or glaucoma, have
occurred with daratumumab-containing products. If ocular symptoms
occur, interrupt DARZALEX FASPRO® and seek
immediate ophthalmologic evaluation prior to restarting DARZALEX
FASPRO®.
Local Reactions
In this pooled safety population,
injection-site reactions occurred in 7% of patients, including
Grade 2 reactions in 0.8%. The most frequent (>1%)
injection-site reaction was injection-site erythema. These local
reactions occurred a median of 5 minutes (range: 0 minutes to
6.5 days) after starting administration of DARZALEX
FASPRO®. Monitor for local reactions and consider
symptomatic management.
Neutropenia
Daratumumab may increase neutropenia
induced by background therapy. Monitor complete blood cell counts
periodically during treatment according to manufacturer's
prescribing information for background therapies. Monitor patients
with neutropenia for signs of infection. Consider withholding
DARZALEX FASPRO® until recovery of neutrophils.
In lower body weight patients receiving DARZALEX
FASPRO®, higher rates of Grade 3-4 neutropenia
were observed.
Thrombocytopenia
Daratumumab may increase
thrombocytopenia induced by background therapy. Monitor complete
blood cell counts periodically during treatment according to
manufacturer's prescribing information for background therapies.
Consider withholding DARZALEX FASPRO® until
recovery of platelets.
Embryo-Fetal Toxicity
Based on the mechanism of
action, DARZALEX FASPRO® can cause fetal harm
when administered to a pregnant woman. DARZALEX
FASPRO® may cause depletion of fetal immune cells
and decreased bone density. Advise pregnant women of the potential
risk to a fetus. Advise females with reproductive potential to use
effective contraception during treatment with DARZALEX
FASPRO® and for 3 months after the last
dose.
The combination of DARZALEX FASPRO® with
lenalidomide, thalidomide, or pomalidomide is contraindicated in
pregnant women because lenalidomide, thalidomide, and pomalidomide
may cause birth defects and death of the unborn child. Refer to the
lenalidomide, thalidomide, or pomalidomide prescribing information
on use during pregnancy.
Interference With Serological Testing
Daratumumab
binds to CD38 on red blood cells (RBCs) and results in a positive
indirect antiglobulin test (indirect Coombs test).
Daratumumab-mediated positive indirect antiglobulin test may
persist for up to 6 months after the last daratumumab
administration. Daratumumab bound to RBCs masks detection of
antibodies to minor antigens in the patient's serum. The
determination of a patient's ABO and Rh blood type are not
impacted.
Notify blood transfusion centers of this interference with
serological testing and inform blood banks that a patient has
received DARZALEX FASPRO®. Type and screen
patients prior to starting DARZALEX
FASPRO®.
Interference With Determination of Complete
Response
Daratumumab is a human immunoglobulin G (IgG) kappa
monoclonal antibody that can be detected on both the serum protein
electrophoresis (SPE) and immunofixation (IFE) assays used for the
clinical monitoring of endogenous M-protein. This interference can
impact the determination of complete response and of disease
progression in some DARZALEX FASPRO®-treated
patients with IgG kappa myeloma protein.
ADVERSE REACTIONS
In multiple myeloma, the most common
adverse reaction (≥20%) with DARZALEX FASPRO®
monotherapy is upper respiratory tract infection. The most
common adverse reactions with combination therapy (≥20% for any
combination) include fatigue, nausea, diarrhea, dyspnea, insomnia,
headache, pyrexia, cough, muscle spasms, back pain, vomiting,
hypertension, upper respiratory tract infection, peripheral
neuropathy, peripheral sensory neuropathy, constipation, pneumonia,
edema, peripheral edema, musculoskeletal pain, and
rash.
The most common hematology laboratory abnormalities (≥40%) with
DARZALEX FASPRO® are decreased leukocytes,
decreased lymphocytes, decreased neutrophils, decreased platelets,
and decreased hemoglobin.
Please click here to read full Prescribing
Information for DARZALEX
FASPRO®.
About Johnson & Johnson
At Johnson &
Johnson, we believe health is everything. Our strength in
healthcare innovation empowers us to build a world where complex
diseases are prevented, treated, and cured, where treatments are
smarter and less invasive, and solutions are personal. Through our
expertise in Innovative Medicine and MedTech, we are uniquely
positioned to innovate across the full spectrum of healthcare
solutions today to deliver the breakthroughs of tomorrow, and
profoundly impact health for humanity. Learn more at
https://www.jnj.com/ or at
www.janssen.com/johnson-johnson-innovative-medicine. Follow us
at @JanssenUS and @JNJInnovMed. Janssen Research &
Development, LLC and Janssen Biotech, Inc. are both Johnson &
Johnson companies.
Cautions Concerning Forward-Looking
Statements
This press release contains
"forward-looking statements" as defined in the Private Securities
Litigation Reform Act of 1995 regarding product development and the
potential benefits and treatment impact of DARZALEX
FASPRO® (daratumumab and hyaluronidase-fihj).
The reader is cautioned not to rely on these forward-looking
statements. These statements are based on current expectations of
future events. If underlying assumptions prove inaccurate or known
or unknown risks or uncertainties materialize, actual results could
vary materially from the expectations and projections of Janssen
Research & Development, LLC, Janssen Biotech, Inc. and/or
Johnson & Johnson. Risks and uncertainties include, but are not
limited to: challenges and uncertainties inherent in product
research and development, including the uncertainty of clinical
success and of obtaining regulatory approvals; uncertainty of
commercial success; manufacturing difficulties and delays;
competition, including technological advances, new products and
patents attained by competitors; challenges to patents; product
efficacy or safety concerns resulting in product recalls or
regulatory action; changes in behavior and spending patterns of
purchasers of health care products and services; changes to
applicable laws and regulations, including global health care
reforms; and trends toward health care cost containment. A further
list and descriptions of these risks, uncertainties and other
factors can be found in Johnson & Johnson's Annual Report on
Form 10-K for the fiscal year ended December
31, 2023, including in the sections captioned "Cautionary
Note Regarding Forward-Looking Statements" and "Item 1A. Risk
Factors," and in Johnson & Johnson's subsequent Quarterly
Reports on Form 10-Q and other filings with the Securities and
Exchange Commission. Copies of these filings are available online
at www.sec.gov, www.jnj.com or on request from Johnson &
Johnson. None of Janssen Research & Development, LLC, Janssen
Biotech, Inc., nor Johnson & Johnson undertake to update any
forward-looking statement as a result of new information or future
events or developments.
*Dr. Saad Z. Usmani has provided
consulting, advisory, and speaking services to Johnson &
Johnson; he has not been paid for any media work.
1 Usmani, S., et al. Daratumumab SC +
Bortezomib/Lenalidomide/Dexamethasone in Patients With
Transplant-ineligible or Transplant-deferred Newly Diagnosed
Multiple Myeloma: Results of the Phase 3 CEPHEUS Study. IMS 2024.
September 27, 2024.
2 Rajkumar SV. Multiple Myeloma: 2020 Update on
Diagnosis, Risk-Stratification and Management. Am J
Hematol.
2020;95(5):548-5672020;95(5):548-567. http://www.ncbi.nlm.nih.gov/pubmed/32212178
3 National Cancer Institute. Plasma Cell Neoplasms.
Accessed July 2024. Available at:
https://www.cancer.gov/types/myeloma/patient/myeloma-treatment-pdq
4 Multiple Myeloma. City of Hope, 2022. Multiple
Myeloma: Causes, Symptoms & Treatments. Accessed July 2024. Available at:
https://www.cancercenter.com/cancer-types/multiple-myeloma
5 American Cancer Society. Myeloma Cancer Statistics.
Accessed July 2024. Available
at: https://cancerstatisticscenter.cancer.org/types/myeloma
6 American Cancer Society. What is Multiple Myeloma?
Accessed July 2024. Available
at: https://www.cancer.org/cancer/multiple-myeloma/about/what-is-multiple-myeloma.html
7 American Cancer Society. Multiple Myeloma Early
Detection, Diagnosis, and Staging. Accessed July 2024. Available at:
https://www.cancer.org/cancer/types/multiple-myeloma/detection-diagnosis-staging/detection.html
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