NORTH CHICAGO, Ill.,
Dec. 7, 2019 /PRNewswire/ -- AbbVie
(NYSE: ABBV), a research-based global biopharmaceutical
company, today announced new data from the Phase 2 CAPTIVATE
(PCYC-1142) clinical trial,1 evaluating
IMBRUVICA® (ibrutinib) in combination with
VENCLEXTA®/VENCLYXTO® (venetoclax) in
previously untreated patients with chronic lymphocytic leukemia
(CLL) or small lymphocytic lymphoma (SLL). Results showed that
patients who received up to 12 cycles of the combination regimen
achieved high rates of undetectable minimal residual disease (uMRD)
in both peripheral blood (PB; 75 percent of patients) and in bone
marrow (BM; 72 percent of patients). Safety data were consistent
with the known safety profiles of IMBRUVICA and VENCLEXTA/VENCLYXTO
used as individual therapies.
According to the Leukemia & Lymphoma Society, MRD refers to
the small number of cancer cells that remain in the body after
treatment. The number of remaining cells may be so small that they
do not cause any physical signs or symptoms and often cannot even
be detected through traditional methods. Doctors use MRD to measure
the effectiveness of treatment and to predict which patients are at
risk of relapse.
"The oral regimen of ibrutinib alone followed by combined
ibrutinib and venetoclax delivered a promising rate of disease
clearance in previously untreated patients with CLL, with 75
percent and 72 percent of patients having undetectable disease
(MRD) in the blood and bone marrow, respectively," said
Constantine Tam, M.D., Hematologist
and Disease Group Lead, Low Grade Lymphoma and CLL at Peter
MacCallum Cancer Centre, Victoria,
Australia, and lead study investigator of CAPTIVATE. "We are
encouraged by these data and the potentially potent combination of
ibrutinib plus venetoclax treatment for CLL and potentially other
blood cancers in the future."
The data were presented today during an oral presentation
session at the 2019 American Society of Hematology (ASH) Annual
Meeting (abstract #35). Results from the MRD-guided, randomized
treatment discontinuation cohort and fixed duration cohort of the
CAPTIVATE clinical trial are currently being evaluated and will be
presented at a future medical meeting.
"While IMBRUVICA and VENCLEXTA/VENCLYXTO-based treatments are
the established standard-of-care for different CLL patients today,
an IMBRUVICA plus VENCLEXTA/VENCLYXTO combination treatment could
be a new and innovative option for patients, as evidenced by the
positive results from the CAPTIVATE clinical trial," said
Mohamed Zaki, M.D., Ph.D., Head of
Hematology Oncology, AbbVie. "We are pleased with the results from
this CLL treatment combination and look forward to sharing
additional analyses in the future."
IMBRUVICA is a once-daily, first-in-class Bruton's tyrosine
kinase (BTK) inhibitor that is administered orally, and is jointly
developed and commercialized by Pharmacyclics LLC, an AbbVie
company, and Janssen Biotech, Inc.
VENCLEXTA/VENCLYXTO is a first-in-class medicine that
selectively binds and inhibits the B-cell lymphoma-2 (BCL-2)
protein. In some blood cancers, BCL-2 prevents cancer cells from
undergoing their natural death or self-destruction process, called
apoptosis. VENCLEXTA/VENCLYXTO targets the BCL-2 protein and works
to help restore the process of apoptosis. VENCLEXTA/VENCLYXTO is
being developed by AbbVie and Roche. It is jointly commercialized
by AbbVie and Genentech, a member of the Roche Group, in the U.S.
and by AbbVie outside of the U.S. Together, the companies are
committed to BCL-2 research and to studying venetoclax in clinical
trials across several blood and other cancers.
Abstract #35: Ibrutinib Plus Venetoclax for First-line
Treatment of Chronic Lymphocytic Leukemia or Small Lymphocytic
Lymphoma (CLL/SLL): Results from Minimal Residual Disease (MRD)
Cohort of Phase 2 CAPTIVATE Study
Oral Presentation: Saturday, December
7 at 8:30 a.m. EST
The Phase 2 CAPTIVATE (PCYC-1142) clinical trial evaluated 164
patients younger than 70 years (median age of 58 years) with
previously untreated CLL/SLL. Ninety-two percent of patients
(n=151) were randomly assigned to receive IMBRUVICA monotherapy as
lead-in treatment for 3 cycles. Following, all patients completed
12 cycles of IMBRUVICA plus VENCLEXTA/VENCLYXTO combination
regimen. MRD status was evaluated in PB after 6, 9, and 12 cycles
and in BM after 12 cycles of IMBRUVICA plus
VENCLEXTA/VENCLYXTO.
Results showed uMRD – defined as less than 1 CLL cell per 10,000
leukocytes (MRD<0.01 percent) by flow cytometry of PB or BM
samples – was achieved at any time after baseline in PB for 75
percent of patients (122 of 163 patients) and in BM for 72 percent
(111 of 155 patients). The proportion of patients who had uMRD in
PB increased over time from 57 percent after 6 cycles, 68 percent
after 9 cycles, and 73 percent after 12 cycles of IMBRUVICA plus
VENCLEXTA/VENCLYXTO. The high rates of uMRD in BM were consistent
across high-risk subgroups, including in patients with del(17p),
del(17p) or TP53 mutation, del(11q), complex karyotype, and
unmutated IGHV status. In patients with uMRD in PB with matched BM
samples, 93 percent of patients had uMRD in both PB and BM. With
median follow-up of 14.7 months, 3 patients (2 percent) experienced
disease progression.
The most common adverse events (AEs) of any grade (in 20 percent
of patients or greater) were diarrhea (31 percent) and arthralgia
(22 percent) during treatment with IMBRUVICA alone; and diarrhea
(60 percent), neutropenia (40 percent), nausea (34 percent), upper
respiratory tract infection (24 percent), and fatigue (20 percent)
during treatment with IMBRUVICA plus VENCLEXTA/VENCLYXTO. AEs
leading to dose reductions occurred in 20 percent of patients
overall (IMBRUVICA: 14 percent; VENCLEXTA/VENCLYXTO: 9 percent).
AEs leading to discontinuation were infrequent, occurring in 5
percent of patients overall (IMBRUVICA: 6 percent;
VENCLEXTA/VENCLYXTO: 4 percent).
About IMBRUVICA® (ibrutinib)
IMBRUVICA (ibrutinib) is an oral, once-daily medicine that works
differently than chemotherapy as it blocks a protein called
Bruton's tyrosine kinase (BTK). The BTK protein sends important
signals that tell B cells to mature and produce antibodies. BTK
signaling is needed by specific cancer cells to multiply and
spread.2.3 By blocking BTK, IMBRUVICA may help move
abnormal B cells out of their nourishing environments in the lymph
nodes, bone marrow, and other organs.4
Since its launch in 2013, IMBRUVICA has received 10 FDA
approvals across six disease areas: chronic lymphocytic leukemia
(CLL) with or without 17p deletion (del17p); small lymphocytic
lymphoma (SLL) with or without del17p; Waldenström's
macroglobulinemia (WM); previously-treated patients with mantle
cell lymphoma (MCL)*; previously-treated patients with marginal
zone lymphoma (MZL) who require systemic therapy and have received
at least one prior anti-CD20-based therapy* – and
previously-treated patients with chronic graft-versus-host disease
(cGVHD) after failure of one or more lines of systemic
therapy.5
IMBRUVICA is now approved in 95 countries and has been used to
treat more than 170,000 patients worldwide across its approved
indications. IMBRUVICA is the only FDA-approved medicine in WM and
cGVHD. IMBRUVICA has been granted four Breakthrough Therapy
Designations from the U.S. FDA. This designation is intended to
expedite the development and review of a potential new drug for
serious or life-threatening diseases. IMBRUVICA was one of the
first medicines to receive FDA approval via the Breakthrough
Therapy Designation pathway.
The NCCN Clinical Practice Guidelines in Oncology (NCCN
Guidelines®) for CLL recommends ibrutinib
(IMBRUVICA®) as a preferred regimen for the initial
treatment of CLL/SLL and it is the only Category 1 single-agent
regimen for treatment-naïve patients without deletion 17p.
IMBRUVICA is being studied alone and in combination with other
treatments in several blood and solid tumor cancers and other
serious illnesses. IMBRUVICA is the most comprehensively studied
BTK inhibitor, with more than 150 ongoing clinical trials. There
are approximately 30 ongoing company-sponsored trials, 14 of which
are in Phase 3, and more than 100 investigator-sponsored trials and
external collaborations that are active around the world. For more
information, visit www.IMBRUVICA.com.
*Accelerated approval was granted for the MCL and MZL
indications based on overall response rate. Continued approval for
MCL and MZL may be contingent upon verification and description of
clinical benefit in confirmatory trials.
IMBRUVICA IMPORTANT
SAFETY INFORMATION
WARNINGS AND PRECAUTIONS
Hemorrhage: Fatal bleeding events have occurred in
patients treated with IMBRUVICA®. Major hemorrhage
(≥ Grade 3, serious, or any central nervous system events;
e.g., intracranial hemorrhage [including subdural hematoma],
gastrointestinal bleeding, hematuria, and post procedural
hemorrhage) have occurred in 4% of patients, with fatalities
occurring in 0.4% of 2,838 patients exposed to
IMBRUVICA® in 27 clinical trials. Bleeding events
of any grade, including bruising and petechiae, occurred in 39% of
patients treated with IMBRUVICA®.
The mechanism for the bleeding events is not well
understood.
Use of either anticoagulant or antiplatelet agents concomitantly
with IMBRUVICA® increases the risk of major hemorrhage.
In IMBRUVICA® clinical trials, 3.1% of patients taking
IMBRUVICA® without antiplatelet or anticoagulant therapy
experienced major hemorrhage. The addition of antiplatelet
therapy with or without anticoagulant therapy increased this
percentage to 4.4%, and the addition of anticoagulant therapy with
or without antiplatelet therapy increased this percentage to
6.1%. Consider the risks and benefits of anticoagulant or
antiplatelet therapy when co-administered with
IMBRUVICA®. Monitor for signs and symptoms of
bleeding.
Consider the benefit-risk of withholding IMBRUVICA®
for at least 3 to 7 days pre- and post-surgery depending upon the
type of surgery and the risk of bleeding.
Infections: Fatal and non-fatal infections
(including bacterial, viral, or fungal) have occurred with
IMBRUVICA® therapy. Grade 3 or greater infections
occurred in 24% of 1,124 patients exposed to IMBRUVICA®
in clinical trials. Cases of progressive multifocal
leukoencephalopathy (PML) and Pneumocystis jirovecii
pneumonia (PJP) have occurred in patients treated with
IMBRUVICA®. Consider prophylaxis according to standard
of care in patients who are at increased risk for opportunistic
infections.
Monitor and evaluate patients for fever and infections and treat
appropriately.
Cytopenias: Treatment-emergent Grade 3 or 4
cytopenias including neutropenia (23%), thrombocytopenia (8%), and
anemia (3%) based on laboratory measurements occurred in patients
with B‑cell malignancies treated with single agent
IMBRUVICA®.
Monitor complete blood counts monthly.
Cardiac Arrhythmias: Fatal and serious cardiac
arrhythmias have occurred with IMBRUVICA® therapy.
Grade 3 or greater ventricular tachyarrhythmias occurred in 0.2% of
patients, and Grade 3 or greater atrial fibrillation and atrial
flutter occurred in 4% of 1,124 patients exposed to
IMBRUVICA® in clinical trials. These events have
occurred particularly in patients with cardiac risk factors,
hypertension, acute infections, and a previous history of cardiac
arrhythmias.
Periodically monitor patients clinically for cardiac
arrhythmias. Obtain an ECG for patients who develop arrhythmic
symptoms (e.g., palpitations, lightheadedness, syncope, chest pain)
or new onset dyspnea. Manage cardiac arrhythmias
appropriately, and if it persists, consider the risks and benefits
of IMBRUVICA® treatment and follow dose modification
guidelines.
Hypertension: Hypertension of any grade occurred in
12% of 1,124 patients treated with IMBRUVICA® in
clinical trials. Grade 3 or greater hypertension occurred in 5% of
patients with a median time to onset of 5.9 months (range, 0.03 to
24 months).
Monitor blood pressure in patients treated with
IMBRUVICA® and initiate or adjust anti-hypertensive
medication throughout treatment with IMBRUVICA® as
appropriate.
Second Primary Malignancies: Other malignancies
(10%) including non-skin carcinomas (4%) have occurred in 1,124
patients treated with IMBRUVICA® in clinical trials. The
most frequent second primary malignancy was non-melanoma skin
cancer (6%).
Tumor Lysis Syndrome: Tumor lysis syndrome has been
infrequently reported with IMBRUVICA® therapy. Assess
the baseline risk (e.g., high tumor burden) and take appropriate
precautions.
Monitor patients closely and treat as appropriate.
Embryo-Fetal Toxicity: Based on findings in animals,
IMBRUVICA® can cause fetal harm when administered to a
pregnant woman. Advise women to avoid becoming pregnant while
taking IMBRUVICA® and for 1 month after cessation of
therapy. If this drug is used during pregnancy or if the patient
becomes pregnant while taking this drug, the patient should be
apprised of the potential hazard to a fetus. Advise men to avoid
fathering a child during the same time period.
ADVERSE REACTIONS
B-cell malignancies: The most common adverse
reactions (≥20%) in patients with B-cell malignancies (MCL,
CLL/SLL, WM and MZL) were thrombocytopenia (58%)*, diarrhea (41%),
anemia (38%)*, neutropenia (35%)*, musculoskeletal pain (32%), rash
(32%), bruising (31%), nausea (26%), fatigue (26%), hemorrhage
(24%), and pyrexia (20%).
The most common Grade 3 or 4 adverse reactions (≥5%) in patients
with B-cell malignancies (MCL, CLL/SLL, WM and MZL) were
neutropenia (18%)*, thrombocytopenia (16%)*, and pneumonia
(14%).
Approximately 7% (CLL/SLL), 14% (MCL), 14% (WM)
and 10% (MZL) of patients had a
dose reduction due to adverse reactions.
Approximately 4-10% (CLL/SLL), 9% (MCL), and
7% (WM [5%] and MZL [13%]) of patients
discontinued due to adverse reactions.
cGVHD: The most common adverse reactions (≥20%) in patients with cGVHD were fatigue (57%), bruising (40%), diarrhea (36%), thrombocytopenia (33%)*, muscle spasms (29%),
stomatitis (29%), nausea (26%),
hemorrhage (26%), anemia (24%)*, and pneumonia
(21%).
The most common Grade 3 or higher adverse reactions (≥5%) reported in patients with cGVHD were
pneumonia (14%), fatigue (12%), diarrhea (10%),
neutropenia (10%)*, sepsis (10%), hypokalemia (7%),
headache (5%), musculoskeletal pain (5%), and pyrexia
(5%).
Twenty-four percent of patients receiving IMBRUVICA® in the
cGVHD trial discontinued treatment due to adverse reactions.
Adverse reactions leading to dose reduction occurred in 26% of
patients.
*Treatment-emergent decreases (all grades) were based on
laboratory measurements.
DRUG INTERACTIONS
CYP3A Inhibitors: Co-administration of
IMBRUVICA® with strong or moderate CYP3A inhibitors may
increase ibrutinib plasma concentrations. Dose modifications of
IMBRUVICA® may be recommended when used concomitantly
with posaconazole, voriconazole, and moderate CYP3A inhibitors.
Avoid concomitant use of other strong CYP3A inhibitors. Interrupt
IMBRUVICA® if strong inhibitors are used short-term
(e.g., for ≤ 7 days). See dose modification guidelines in USPI
sections 2.4 and 7.1.
CYP3A Inducers: Avoid coadministration with strong CYP3A
inducers.
SPECIFIC POPULATIONS
Hepatic Impairment (based on Child-Pugh criteria): Avoid
use of IMBRUVICA® in patients with severe baseline
hepatic impairment. In patients with mild or moderate impairment,
reduce IMBRUVICA® dose.
Please click here
for full Prescribing Information.
About VENCLEXTA®/VENCLYXTO®
(venetoclax)
VENCLEXTA®/VENCLYXTO® (venetoclax) is a
first-in-class medicine that selectively binds and inhibits the
B-cell lymphoma-2 (BCL-2) protein. In some blood cancers, BCL-2
prevents cancer cells from undergoing their natural death or
self-destruction process, called apoptosis. VENCLEXTA/VENCLYXTO
targets the BCL-2 protein and works to help restore the process of
apoptosis.
VENCLEXTA/VENCLYXTO is being developed by AbbVie and Roche. It
is jointly commercialized by AbbVie and Genentech, a member of the
Roche Group, in the U.S. and by AbbVie outside of the U.S.
Together, the companies are committed to BCL-2 research and to
studying venetoclax in clinical trials across several blood and
other cancers.
VENCLEXTA/VENCLYXTO is approved in more than 50 countries,
including the U.S. AbbVie, in collaboration with Roche, is
currently working with regulatory agencies around the world to
bring this medicine to additional eligible patients in need.
VENCLEXTA/VENCLYXTO is approved in more than 50 countries,
including the U.S. AbbVie, in collaboration with Roche, is
currently working with regulatory agencies around the world to
bring this medicine to additional eligible patients in need.
Uses and Important
VENCLEXTA® (venetoclax) U.S. Safety
Information6
Uses
VENCLEXTA is a prescription medicine used:
- to treat adults with chronic lymphocytic leukemia (CLL) or
small lymphocytic lymphoma (SLL).
- in combination with azacitidine, or decitabine, or low-dose
cytarabine to treat adults with newly-diagnosed acute myeloid
leukemia (AML) who:
-
- are 75 years of age or older, or
- have other medical conditions that prevent the use of standard
chemotherapy.
VENCLEXTA was approved based on
response rates. Continued approval for this use may depend on the
results of an ongoing study to find out how VENCLEXTA works over a
longer period of time.
It is not known if VENCLEXTA is safe and effective in
children.
Important Safety Information
What is the most important information I should know about
VENCLEXTA?
VENCLEXTA can cause serious side effects, including:
Tumor lysis syndrome (TLS). TLS is caused by the fast
breakdown of cancer cells. TLS can cause kidney failure, the need
for dialysis treatment, and may lead to death. Your healthcare
provider will do tests to check your risk of getting TLS before you
start taking VENCLEXTA. You will receive other medicines before
starting and during treatment with VENCLEXTA to help reduce your
risk of TLS. You may also need to receive intravenous (IV)
fluids into your vein. Your healthcare provider will do blood
tests to check for TLS when you first start treatment and during
treatment with VENCLEXTA. It is important to keep your appointments
for blood tests. Tell your healthcare provider right away if you
have any symptoms of TLS during treatment with VENCLEXTA, including
fever, chills, nausea, vomiting, confusion, shortness of breath,
seizures, irregular heartbeat, dark or cloudy urine, unusual
tiredness, or muscle or joint pain.
Drink plenty of water during treatment with VENCLEXTA to help
reduce your risk of getting TLS. Drink 6 to 8 glasses (about 56
ounces total) of water each day, starting 2 days before your first
dose, on the day of your first dose of VENCLEXTA, and each time
your dose is increased.
Your healthcare provider may delay, decrease your dose, or stop
treatment with VENCLEXTA if you have side effects.
Who should not take VENCLEXTA?
Certain medicines must not be taken when you first start
taking VENCLEXTA and while your dose is being slowly increased
because of the risk of increased TLS.
- Tell your healthcare provider about all the medicines you
take, including prescription and over-the- counter medicines,
vitamins, and herbal supplements. VENCLEXTA and other medicines may
affect each other causing serious side effects.
- Do not start new medicines during treatment with VENCLEXTA
without first talking with your healthcare provider.
Before taking VENCLEXTA, tell your healthcare provider about
all of your medical conditions, including if you:
- have kidney or liver problems.
- have problems with your body salts or electrolytes, such as
potassium, phosphorus, or calcium.
- have a history of high uric acid levels in your blood or
gout.
- are scheduled to receive a vaccine. You should not receive a
"live vaccine" before, during, or after treatment with VENCLEXTA,
until your healthcare provider tells you it is okay. If you are not
sure about the type of immunization or vaccine, ask your healthcare
provider. These vaccines may not be safe or may not work as well
during treatment with VENCLEXTA.
- are pregnant or plan to become pregnant. VENCLEXTA may harm
your unborn baby. If you are able to become pregnant, your
healthcare provider should do a pregnancy test before you start
treatment with VENCLEXTA, and you should use effective birth
control during treatment and for at least 30 days after the last
dose of VENCLEXTA. If you become pregnant or think you are
pregnant, tell your healthcare provider right away.
- are breastfeeding or plan to breastfeed. It is not known if
VENCLEXTA passes into your breast milk. Do not breastfeed during
treatment with VENCLEXTA.
What should I avoid while taking VENCLEXTA?
You should not drink grapefruit juice or eat grapefruit,
Seville oranges (often used in
marmalades), or starfruit while you are taking VENCLEXTA. These
products may increase the amount of VENCLEXTA in your blood.
What are the possible side effects of VENCLEXTA?
VENCLEXTA can cause serious side effects, including:
- Low white blood cell counts (neutropenia). Low white
blood cell counts are common with VENCLEXTA, but can also be
severe. Your healthcare provider will do blood tests to check your
blood counts during treatment with VENCLEXTA.
- Infections. Death and serious infections such as
pneumonia and blood infection (sepsis) have happened during
treatment with VENCLEXTA. Your healthcare provider will closely
monitor and treat you right away if you have a fever or any signs
of infection during treatment with VENCLEXTA.
Tell your healthcare provider right away if you have a fever or
any signs of an infection during treatment with VENCLEXTA.
The most common side effects of VENCLEXTA when used in
combination with obinutuzumab or rituximab or alone in people with
CLL or SLL include low white blood cell counts; low
platelet counts; low red blood cell counts; diarrhea; nausea; upper
respiratory tract infection; cough; muscle and joint pain;
tiredness; and swelling of your arms, legs, hands, and feet.
The most common side effects of VENCLEXTA in combination with
azacitidine or decitabine or low-dose cytarabine in people with AML
include low white blood cell counts; nausea; diarrhea; low
platelet counts; constipation; fever with low white blood cell
counts; low red blood cell counts; infection in blood; rash;
dizziness; low blood pressure; fever; swelling of your arms, legs,
hands, and feet; vomiting; tiredness; shortness of breath;
bleeding; infection in lung; stomach (abdominal) pain; pain in
muscles or back; cough; and sore throat.
VENCLEXTA may cause fertility problems in males. This may affect
your ability to father a child. Talk to your healthcare provider if
you have concerns about fertility.
These are not all the possible side effects of VENCLEXTA. For
more information, ask your healthcare provider or pharmacist.
You are encouraged to report negative side effects of
prescription drugs to the FDA. Visit www.fda.gov/medwatch or call
1-800-FDA-1088.
If you cannot afford your medication, contact
www.medicineassistancetool.org for assistance.
The full U.S. prescribing information, including Medication
Guide, for VENCLEXTA can be found here.
Indication and Important VENCLYXTO (venetoclax) EU Safety
Information7
Indication
Venclyxto in combination with rituximab is
indicated for the treatment of adult patients with chronic
lymphocytic leukaemia (CLL) who have received at least one prior
therapy.
Venclyxto monotherapy is indicated for the treatment of CLL:
- in the presence of 17p deletion or TP53 mutation in adult
patients who are unsuitable for or have failed a B-cell receptor
pathway inhibitor, or
- in the absence of 17p deletion or TP53 mutation in adult
patients who have failed both chemoimmunotherapy and a B-cell
receptor pathway inhibitor.
Contraindications
Hypersensitivity to the active
substance or to any of the excipients is contraindicated.
Concomitant use of strong CYP3A inhibitors at initiation and during
the dose-titration phase due to increased risk for tumor lysis
syndrome (TLS). Concomitant use of preparations containing
St. John's wort as VENCLYXTO
efficacy may be reduced.
Special Warnings & Precautions for Use
Tumor lysis
syndrome (TLS), including fatal events, has occurred in patients
with previously treated CLL with high tumor burden when treated
with VENCLYXTO. VENCLYXTO poses a risk for TLS in the initial
5-week dose-titration phase. Changes in electrolytes consistent
with TLS that require prompt management can occur as early as 6 to
8 hours following the first dose of VENCLYXTO and at each dose
increase. Patients should be assessed for risk and should receive
appropriate prophylaxis, monitoring, and management for TLS.
Neutropenia (grade 3 or 4) has been reported and complete blood
counts should be monitored throughout the treatment period. Serious
infections including events of sepsis with fatal outcome have been
reported. Supportive measures including antimicrobials for any
signs of infection should be considered.
Live vaccines should not be administered during treatment or
thereafter until B-cell recovery.
Drug Interactions
CYP3A inhibitors may increase
VENCLYXTO plasma concentrations. At initiation and dose-titration
phase: Strong CYP3A inhibitors are contraindicated due to increased
risk for TLS and moderate CYP3A inhibitors should be avoided. If
moderate CYP3A inhibitors must be used, physicians should refer to
the SmPC for dose adjustment recommendations. At steady daily dose:
If moderate or strong CYP3A inhibitors must be used, physicians
should refer to the SmPC for dose adjustment recommendations.
Avoid concomitant use of P-gp and BCRP inhibitors at initiation
and during the dose titration phase.
CYP3A4 inducers may decrease VENCLYXTO plasma concentrations.
Avoid coadministration with strong or moderate CYP3A inducers.
These agents may decrease venetoclax plasma
concentrations.
Co-administration of bile acid sequestrants with VENCLYXTO is
not recommended as this may reduce the absorption of VENCLYXTO.
Adverse Reactions
The most commonly occurring adverse
reactions (>=20%) of any grade in patients receiving venetoclax
in the combination study with rituximab were neutropenia, diarrhea,
and upper respiratory tract infection. In the monotherapy studies,
the most common adverse reactions were neutropenia/neutrophil count
decreased, diarrhea, nausea, anemia, fatigue, and upper respiratory
tract infection.
The most frequently occurring serious adverse reactions
(>=2%) in patients receiving venetoclax in combination with
rituximab or as monotherapy were pneumonia, febrile neutropenia and
TLS.
Discontinuation due to adverse reactions occurred in 16% of
patients receiving venetoclax plus rituximab and 9% receiving
venetoclax monotherapy. Dosage adjustments due to adverse
reactions occurred in 15% of patients receiving venetoclax plus
rituximab and 2% receiving venetoclax monotherapy. Dose
interruptions occurred in 71% of patients treated with the
combination of venetoclax and rituximab.
Specific Populations
Patients with reduced renal
function (CrCl <80 mL/min) may require more intensive
prophylaxis and monitoring to reduce the risk of TLS. Safety in
patients with severe renal impairment (CrCl <30 mL/min) or on
dialysis has not been established, and a recommended dose for these
patients has not been determined. For patients with severe
(Child-Pugh C) hepatic impairment, a dose reduction of at
least 50% throughout treatment is recommended.
VENCLYXTO may cause embryo-fetal harm when administered to a
pregnant woman. Advise nursing women to discontinue breastfeeding
during treatment.
This is not a complete summary of all safety information. See
VENCLYXTO full summary of product characteristics (SmPC) at
www.ema.europa.eu. Globally, prescribing information
varies; refer to the individual country product label for complete
information.
About AbbVie in Oncology
At AbbVie, we strive to
discover and develop medicines that deliver transformational
improvements in cancer treatment by uniquely combining our deep
knowledge in core areas of biology with cutting-edge technologies,
and by working together with our partners – scientists, clinical
experts, industry peers, advocates, and patients. We remain focused
on delivering these transformative advances in treatment across
some of the most debilitating and widespread cancers. We are also
committed to exploring solutions to help patients obtain access to
our cancer medicines. AbbVie's oncology portfolio now consists of
marketed medicines and a pipeline containing multiple new molecules
being evaluated worldwide in more than 300 clinical trials and more
than 20 different tumor types. For more information, please visit
http://www.abbvie.com/oncology.
About AbbVie
AbbVie is a global, research and
development-based biopharmaceutical company committed to developing
innovative advanced therapies for some of the world's most complex
and critical conditions. The company's mission is to use its
expertise, dedicated people and unique approach to innovation to
markedly improve treatments across four primary therapeutic areas:
immunology, oncology, virology and neuroscience. In more than
75 countries, AbbVie employees are working every day to advance
health solutions for people around the world. For more information
about AbbVie, please visit us at www.abbvie.com. Follow @abbvie on
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news release are, or may be considered, forward-looking statements
for purposes of the Private Securities Litigation Reform Act of
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similar expressions, among others, generally identify
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that may cause actual results to differ materially from those
indicated in the forward-looking statements. Such risks and
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litigation or government action, and changes to laws and
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