New analysis from Phase 3 CEPHEUS study demonstrates 85
percent of patients who achieved MRD negativity
(10-6) with DARZALEX
FASPRO® were progression free at 4.5
years
Subgroup analysis from Phase 3 AURIGA study show higher rates
of MRD-negative conversion in patient populations
disproportionately impacted by multiple myeloma
SAN
DIEGO, Dec. 8, 2024 /PRNewswire/ -- Johnson &
Johnson (NYSE: JNJ) today announced data highlighting that DARZALEX
FASPRO® (daratumumab and
hyaluronidase-fihj)-based regimens improve overall and sustained
minimal residual disease (MRD) negativity rates and
progression-free survival (PFS) in patients with newly diagnosed
multiple myeloma (NDMM), regardless of transplant
status.1,2 These findings were demonstrated in an
expanded MRD analysis of the Phase 3 CEPHEUS study (Abstract #362)
and a post hoc analysis of clinically relevant subgroups in the
Phase 3 AURIGA study (Abstract #675), which were both featured as
oral presentations at the 2024 American Society of Hematology (ASH)
Annual Meeting.
Data from the expanded MRD analysis of the Phase 3 CEPHEUS study
show the addition of DARZALEX FASPRO® to
bortezomib, lenalidomide and dexamethasone (D-VRd) leads to
improved and deepened rates of overall and sustained MRD negativity
(both 10-5 and 10-6 sensitivity thresholds in
patients who achieved a complete response or better) versus VRd
alone, and shows significantly improved progression-free
survival.1 CEPHEUS is the fifth Phase 3 study
showing the addition of DARZALEX® improves depth
and duration of response, leading to improved progression-free
survival.1,3,4,5
At a median follow-up of 58.7 months, overall MRD-negativity
rates were significantly higher with D-VRd versus VRd at both
10–5 (60.9 percent vs. 39.4 percent; odds ratio [OR],
2.37; 95 percent confidence interval [CI], 1.58-3.55;
P<0.0001) and 10–6 (46.2 percent vs. 27.3
percent; OR, 2.24; 95 percent CI, 1.48-3.40; P=0.0001)
sensitivity thresholds. Treatment with D-VRd shows continued
benefit of sustained MRD negativity for two years (10-5:
42.1 percent vs. 22.7 percent; 10-6: 27.9 percent vs.
13.6 percent). Additionally, the deeper and more sustained MRD
negativity rates with D-VRd trended with improved progression-free
survival (PFS) rates – the estimated 54-month PFS rates were 86.2
percent for D-VRd patients versus 79 percent for VRd in MRD
negative (10-6) patients, and 51 percent versus 36.5
percent for MRD-positive patients.1
"This analysis from the CEPHEUS study comparing daratumumab-VRd
versus VRd, showed higher rates of both overall and sustained MRD
negativity alongside promising trends in progression-free
survival," said Sonja Zweegman, MD,
PhD, head of the Department of Hematology, Amsterdam University
Medical Center.* "This regimen has the potential to improve
outcomes for patients with newly diagnosed multiple myeloma who are
ineligible for transplant or for whom transplant is not planned as
initial therapy."
Addition of DARZALEX FASPRO® to maintenance
regimens resulted in higher MRD negativity rates across clinically
relevant subgroups by age, race, disease stage and cytogenetic
risk
In a post hoc analysis of the Phase 3 AURIGA study, an
investigational maintenance regimen of DARZALEX
FASPRO® combined with lenalidomide
(R) resulted in consistently improved MRD-negative conversion rates
after 12 months. These results were consistent across anti-CD38
naïve patient subgroups who were MRD-positive post-autologous stem
cell transplant (ASCT). In patients older than 65 years,
MRD-negative rates were higher when treated with D-R maintenance
therapy compared to R alone (52.6 percent vs. 17.5 percent; OR,
5.24; 95 percent CI, 1.86-14.74). Maintenance therapy with D-R
showed a consistently higher conversion to MRD negativity in Black
patients (n=20) compared to R alone (60.0 percent vs 16.7 percent;
OR, 7.50; 95 percent CI, 1.85-30.34) and white patients (n=67)
(46.3 percent vs. 20.6 percent; OR, 3.32; 95 percent CI,
1.55-7.10).2
Data also show that the investigational maintenance regimen of
D-R resulted in higher MRD-negative conversion rates for
patients with advanced-stage disease (Stage III) as defined by the
International Staging System (ISS) (65.2 percent vs. 13 percent;
OR, 12.50; 95 percent CI, 2.83-55.25) and patients with high
cytogenetic risk per the standard definition (31.8 percent vs. 6.7
percent; OR, 6.53; 95% CI, 0.71-60.05) or the revised
definition (43.8 percent vs. 13.3 percent; OR, 5.06; 95 percent CI,
1.43-17.88).2
"Patients over 65, Black individuals, and those with advanced or
high-risk disease are disproportionately impacted by multiple
myeloma and historically have had fewer treatment options that
yield deep and durable results," said Imran
Khan, M.D., Ph.D., Vice President, Medical Affairs,
Hematology, Johnson & Johnson Innovative Medicine. "Evaluating
MRD negativity in these patients underlies its importance as a
recognized predictor of long-term progression-free survival. The
data being presented at ASH this year emphasize the potential of
DARZALEX FASPRO in helping newly diagnosed patients achieve
MRD negativity."
Final analysis of Phase 3 ANDROMEDA study reinforces DARZALEX
FASPRO®-based regimen showing significant overall
survival in patients with newly diagnosed light chain (AL)
amyloidosis
The final analysis of the Phase 3 ANDROMEDA study was also
presented (Abstract #891), showing that the addition of
DARZALEX FASPRO® to bortezomib, cyclophosphamide,
and dexamethasone (D-VCd) demonstrated deeper and more rapid
hematologic responses, resulting in a statistically significant
improvement in both OS and major organ deterioration
progression-free survival (MOD-PFS) (i.e., end-stage renal or
cardiac disease, hematologic progression, or death) for patients
with newly diagnosed AL amyloidosis, a rare plasma cell disorder
associated with the deterioration of vital organs. Patients treated
with D-VCd showed a 56 percent reduction in the risk of progression
or death (hazard ratio [HR] = 0.44, P< 0.0001). The
median MOD-PFS was not reached for D-VCd, while it was 30.2 months
for VCd. Additionally, D-VCd also provided significant survival
benefits with a HR of 0.62 (P=0.0121), indicating a 38
percent reduction in the risk of death compared to VCd. The 5-year
survival rate was 76.1 percent for D-VCd versus 64.7 percent for
VCd.6
In the CEPHEUS, AURIGA and ANDROMEDA studies, the safety
profiles were consistent with the known safety profile for
DARZALEX FASPRO®.
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 who
are transplant-ineligible or for whom transplant is not intended as
initial therapy. Primary endpoint is MRD negativity rate at
10-5 sensitivity threshold. Secondary endpoints
include PFS, MRD-negative rate at one year, durable MRD negativity,
ORR, time to and duration of response, PFS on next line of therapy,
overall survival and safety. The trial has enrolled 396 patients in
13 countries.
About the AURIGA Study
The randomized study (NCT03901963) included 200 patients aged 18-79
years with newly diagnosed multiple myeloma who are minimal
residual disease (MRD)-positive after frontline autologous stem
cell transplant. Patients received investigational 1,800 milligram
(mg) daratumumab by subcutaneous (SC) injection in combination with
lenalidomide (orally) as maintenance therapy for a maximum of 36
cycles. Each cycle is 28 days. Patients in the comparative arm will
receive lenalidomide (orally) alone as maintenance therapy for a
maximum of 36 cycles. Each cycle is 28 days.4
About the ANDROMEDA Study
ANDROMEDA (NCT03201965) is an ongoing Phase 3, randomized,
open-label study investigating the safety and efficacy of
DARZALEX FASPRO® (daratumumab and
hyaluronidase-fihj) in combination with bortezomib,
cyclophosphamide and dexamethasone (D-VCd), compared to VCd alone,
for the treatment of adult patients with newly diagnosed light
chain (AL) amyloidosis. The study includes 388 patients with newly
diagnosed AL amyloidosis with measurable hematologic disease and
one or more organs affected. The primary endpoint is overall
complete hematologic response rate by intent-to-treat (ITT).
Patients received
DARZALEX FASPRO® 1,800 mg/30,000 units
administered subcutaneously once weekly from weeks one to eight,
once every two weeks from weeks nine to 24 and once every four
weeks starting with week 25 until disease progression or
unacceptable toxicity or a maximum of two years. Among patients who
received D-VCd, 74 percent were exposed for 6 months or longer and
32 percent were exposed for greater than one year.
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.7 In multiple myeloma, these malignant plasma
cells proliferate and replace normal cells in the bone
marrow.8 Multiple myeloma is the second most common
blood cancer worldwide and remains an incurable
disease.9 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.10 People
with multiple myeloma have a 5-year survival rate of 59.8 percent.
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.11,12
About AL Amyloidosis
Light chain (AL) amyloidosis is a rare and potentially fatal
hematologic disorder that can affect the function of multiple
organs. The disease occurs when bone marrow produces abnormal
pieces of antibodies called light chains, which clump together to
form a substance called amyloid. These clumps of amyloid are
deposited in tissues and vital organs and interfere with normal
organ function, eventually causing organ
deterioration.13,14 It is the most common type of
amyloidosis. AL amyloidosis frequently affects the heart, kidneys,
digestive tract, liver and nervous system, and is potentially fatal
if left untreated.15 Diagnosis is often delayed and
prognosis is poor due to advanced, multi-organ, particularly
cardiac, involvement.16,17 Each year, an estimated
4,500 people develop AL amyloidosis in the U.S.
alone.18
About DARZALEX FASPRO® and
DARZALEX®
DARZALEX FASPRO® (daratumumab and
hyaluronidase-fihj) received U.S. FDA approval in May
2020 and is approved for eight indications in multiple myeloma,
three of which are for frontline treatment in newly diagnosed
patients who are transplant eligible or
ineligible.14 It is the only subcutaneous
CD38-directed antibody approved to treat patients with MM.
DARZALEX FASPRO® is co-formulated with
recombinant human hyaluronidase PH20 (rHuPH20), Halozyme's
ENHANZE® drug delivery technology.
DARZALEX® (daratumumab) received U.S. FDA
approval in November 2015 and is approved in eight
indications, three of which are in the frontline setting, including
newly diagnosed patients who are transplant eligible and
ineligible.6
DARZALEX® is the first CD38-directed antibody
approved to treat multiple
myeloma.6 DARZALEX®-based regimens have
been used in the treatment of more than 580,000 patients worldwide
and more than 239,000 patients in the U.S. alone.
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.
Since 2020, the National Comprehensive Cancer
Network® (NCCN®) has recommended
daratumumab-based combination regimens for the treatment of newly
diagnosed multiple myeloma and relapsed and refractory multiple
myeloma.† For newly diagnosed multiple myeloma in
non-transplant candidates, the NCCN® guidelines
recommend daratumumab in combination with lenalidomide and
dexamethasone as a Category 1 preferred regimen; daratumumab in
combination with bortezomib, melphalan, and prednisone as another
recommended Category 1 regimen; and daratumumab in combination with
bortezomib, cyclophosphamide, and prednisone as another recommended
Category 2A regimen. For newly diagnosed multiple myeloma in
transplant candidates, the NCCN® guidelines
recommend daratumumab in combination with bortezomib, lenalidomide
and dexamethasone as another recommended Category 2A regimen;
daratumumab in combination with bortezomib, thalidomide and
dexamethasone as a Category 2A regimen useful in certain
circumstances; daratumumab in combination with carfilzomib,
lenalidomide and dexamethasone as a Category 2A regimen useful in
certain circumstances; and daratumumab in combination with
cyclophosphamide, bortezomib and dexamethasone as a Category 2A
regimen useful in certain circumstances. For maintenance in
transplant candidates, the NCCN guidelines recommend daratumumab in
combination with lenalidomide as useful in certain circumstances.
In relapsed/refractory myeloma, four daratumumab regimens are
listed as Category 1 preferred regimens for early relapses (1-3
prior therapies): daratumumab in combination with lenalidomide and
dexamethasone; daratumumab in combination with bortezomib and
dexamethasone; daratumumab in combination with carfilzomib and
dexamethasone; and daratumumab in combination with pomalidomide and
dexamethasone [after one prior therapy including lenalidomide and a
proteasome inhibitor (PI)]. The NCCN® also
recommends daratumumab in combination with cyclophosphamide,
bortezomib and dexamethasone as another Category 2A regimen for
early relapses (1-3 prior therapies) and as monotherapy as a
Category 2A regimen useful in certain circumstances for early
relapse patients after at least three prior therapies, including a
PI and an immunomodulatory agent, or for patients who are double
refractory to a PI and an immunomodulatory agent.
For more information, visit www.DARZALEX.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
DARZALEX FASPRO® (daratumumab and
hyaluronidase-fihj) is indicated for the treatment of adult
patients with light chain (AL) amyloidosis
• In combination with bortezomib, cyclophosphamide and
dexamethasone in newly diagnosed patients. This indication is
approved under accelerated approval based on response rate.
Continued approval for this indication may be contingent upon
verification and description of clinical benefit in a confirmatory
trial(s).
Limitations of Use:
DARZALEX FASPRO is not indicated and is not recommended for the
treatment of patients with light chain (AL) amyloidosis who have
NYHA Class IIIB or Class IV cardiac disease or Mayo Stage IIIB
outside of controlled clinical trials.
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.
Cardiac Toxicity in Patients with Light Chain (AL)
Amyloidosis
Serious or fatal cardiac adverse reactions occurred in patients
with light chain (AL) amyloidosis who received DARZALEX FASPRO in
combination with bortezomib, cyclophosphamide and dexamethasone
[see Adverse Reactions (6.1)]. Serious cardiac disorders occurred
in 16% and fatal cardiac disorders occurred in 10% of patients.
Patients with NYHA Class IIIA or Mayo Stage IIIA disease may be at
greater risk. Patients with NYHA Class IIIB or IV disease were not
studied. Monitor patients with cardiac involvement of light
chain (AL) amyloidosis more frequently for cardiac adverse
reactions and administer supportive care as appropriate.
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 sensory neuropathy, constipation,
pneumonia, and peripheral edema.
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 see the full
Prescribing Information for DARZALEX
FASPRO®.
DARZALEX® INDICATIONS AND IMPORTANT SAFETY
INFORMATION
INDICATIONS
DARZALEX® (daratumumab) is indicated for the
treatment of adult patients with multiple myeloma:
• 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
• 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 proteasome inhibitor (PI)
and an immunomodulatory agent or who are double-refractory to a PI
and an immunomodulatory agent
CONTRAINDICATIONS
DARZALEX® is contraindicated in patients with a
history of severe hypersensitivity (eg, anaphylactic reactions) to
daratumumab or any of the components of the formulation.
WARNINGS AND PRECAUTIONS
Infusion-Related Reactions
DARZALEX® can cause severe and/or serious
infusion-related reactions including anaphylactic reactions. These
reactions can be lifethreatening, and fatal outcomes have been
reported. In clinical trials (monotherapy and combination: N=2066),
infusion-related reactions occurred in 37% of patients with the
Week 1 (16 mg/kg) infusion, 2% with the Week 2 infusion, and
cumulatively 6% with subsequent infusions. Less than 1% of patients
had a Grade 3/4 infusion-related reaction at Week 2 or subsequent
infusions. The median time to onset was 1.5 hours (range: 0 to 73
hours). Nearly all reactions occurred during infusion or within 4
hours of completing DARZALEX®. Severe reactions have
occurred, including bronchospasm, hypoxia, dyspnea, hypertension,
tachycardia, headache, laryngeal edema, pulmonary edema, and ocular
adverse reactions, including choroidal effusion, acute myopia, and
acute angle closure glaucoma. Signs and symptoms may include
respiratory symptoms, such as nasal congestion, cough, throat
irritation, as well as chills, vomiting, and nausea. Less common
signs and symptoms were wheezing, allergic rhinitis, pyrexia, chest
discomfort, pruritus, hypotension and blurred vision.
When DARZALEX® dosing was interrupted in the setting
of ASCT (CASSIOPEIA) for a median of 3.75 months (range: 2.4 to 6.9
months), upon re-initiation of DARZALEX®, the incidence
of infusion-related reactions was 11% for the first infusion
following ASCT. Infusion-related reactions occurring at
re-initiation of DARZALEX® following ASCT were
consistent in terms of symptoms and severity (Grade 3 or 4: <1%)
with those reported in previous studies at Week 2 or subsequent
infusions. In EQUULEUS, patients receiving combination treatment
(n=97) were administered the first 16 mg/kg dose at Week 1 split
over two days, ie, 8 mg/kg on Day 1 and Day 2, respectively. The
incidence of any grade infusion-related reactions was 42%, with 36%
of patients experiencing infusion-related reactions on Day 1 of
Week 1, 4% on Day 2 of Week 1, and 8% with subsequent
infusions.
Pre-medicate patients with antihistamines, antipyretics, and
corticosteroids. Frequently monitor patients during the entire
infusion. Interrupt DARZALEX® infusion for reactions of
any severity and institute medical management as needed.
Permanently discontinue DARZALEX® therapy if an
anaphylactic reaction or life-threatening (Grade 4) reaction occurs
and institute appropriate emergency care. For patients with Grade
1, 2, or 3 reactions, reduce the infusion rate when re-starting the
infusion.
To reduce the risk of delayed infusion-related reactions,
administer oral corticosteroids to all patients following
DARZALEX® infusions. Patients with a history of chronic
obstructive pulmonary disease may require additional post-infusion
medications to manage respiratory complications. Consider
prescribing short- and long-acting bronchodilators and inhaled
corticosteroids for patients with chronic obstructive pulmonary
disease.
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 DARZALEX® infusion. If ocular symptoms
occur, interrupt DARZALEX® infusion and seek immediate
ophthalmologic evaluation prior to restarting
DARZALEX®.
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 infusion.
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 is not impacted. Notify blood transfusion
centers of this interference with serological testing and inform
blood banks that a patient has received DARZALEX®. Type
and screen patients prior to starting DARZALEX®.
Neutropenia and Thrombocytopenia
DARZALEX® may increase neutropenia and
thrombocytopenia 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® until recovery of neutrophils or
for recovery of platelets.
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 patients with IgG kappa myeloma protein.
Embryo-Fetal Toxicity
Based on the mechanism of action, DARZALEX® can cause
fetal harm when administered to a pregnant woman.
DARZALEX® 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®
and for 3 months after the last dose.
The combination of DARZALEX® with lenalidomide,
pomalidomide, or thalidomide is contraindicated in pregnant women
because lenalidomide, pomalidomide, and thalidomide may cause birth
defects and death of the unborn child. Refer to the lenalidomide,
pomalidomide, or thalidomide prescribing information on use during
pregnancy.
ADVERSE REACTIONS
The most frequently reported adverse reactions (incidence ≥20%)
were: upper respiratory infection, neutropenia, infusion related
reactions, thrombocytopenia, diarrhea, constipation, anemia,
peripheral sensory neuropathy, fatigue, peripheral edema, nausea,
cough, pyrexia, dyspnea, and asthenia. The most common hematologic
laboratory abnormalities (≥40%) with DARZALEX® are:
neutropenia, lymphopenia, thrombocytopenia, leukopenia, and
anemia.
Please click here to see the full Prescribing
Information.
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.innovativemedicine.jnj.com.
Follow us at @JanssenUS and @JNJInnovMed. Janssen Research
& Development, LLC,Janssen Biotech, Inc..,Janssen Global
Services, LLC and Janssen Scientific Affairs, LLC are 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® (daratumumab)
and 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., Janssen Global Services, LLC, Janssen Scientific
Affairs, LLC 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., Janssen Global
Services, LLC, Janssen Scientific Affairs, LLC nor Johnson &
Johnson undertake to update any forward-looking statement as a
result of new information or future events or
developments.
* Sonja
Zweegman, M.D., Ph.D., head of the Department of Hematology,
VU University Medical Center, has provided consulting, advisory,
and speaking services to Johnson & Johnson; she has not been
paid for any media work.
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