NORTH CHICAGO, Ill.,
May 15, 2020 /PRNewswire/ -- AbbVie
(NYSE: ABBV), a research-based global biopharmaceutical company,
today announced it will present data from studies evaluating the
BCL-2 inhibitor venetoclax (VENCLEXTA®/ VENCLYXTO®), among
others, from clinical trials across multiple blood cancers at the
25th European Hematology Association (EHA) Annual
Congress, being held virtually from June
11-14, 2020. These data will span the company's
investigational and approved oncology portfolio
medicines across chronic lymphocytic leukemia (CLL), acute
myeloid leukemia (AML), acute lymphocytic leukemia (ALL), multiple
myeloma (MM), myelodysplastic syndrome (MDS) and myelofibrosis
(MF).
"We continue to demonstrate the broad utility of our oncology
portfolio – anchored by VENCLEXTA/VENCLYXTO and IMBRUVICA – with
new, longer-term and clinically meaningful results presented at
this year's EHA meeting," said Neil
Gallagher, M.D., Ph.D., chief medical officer and vice
president of development, AbbVie. "We are excited to share these
studies with the global oncology community as they reflect our
ongoing commitment to improving care for patients with various
difficult-to-treat blood cancers."
Researchers will present during EHA data based on findings from
the Phase 3 CLL14 trial evaluating venetoclax in combination with
obinutuzumab in patients with previously-untreated CLL (abstract
#S155). In March 2020, AbbVie
announced the approval of venetoclax plus obinutuzumab in the
European Union, based on data from the CLL14
trial.1 Additionally, several abstracts from
studies of venetoclax in various tumor types will be
presented, including:
- Extended follow-up data from the Phase 3 MURANO trial on
subgroup-analyses of venetoclax in combination with rituximab in
relapsed/refractory CLL, including the impact of premature
discontinuation/interruption of venetoclax on outcomes in these
patients (abstracts #EP694 and #EP691)
- New data on safety and efficacy will be featured from the
CAPTIVATE study evaluating ibrutinib (IMBRUVICA®) plus venetoclax
in first-line treatment of CLL (abstract #S158)
- Six-month update from the Phase 3 VIALE-C study of venetoclax
in combination with low-dose cytarabine in previously untreated
older patients with AML (abstract #S136)
AbbVie sponsored abstracts accepted by EHA include:
Abstract
|
Session+
|
Ibrutinib
|
First-Line Ibrutinib
(Ibr) + Venetoclax (VEN) For Patients (Pts) With Chronic
Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL):
Efficacy And Safety Results From CAPTIVATE-MRD Study. Siddiqi et
al. Abstract #S158
|
Oral Session: CLL –
Targeted Therapy I
|
Ibrutinib Treatment
For Pediatric Chronic Graft Versus Host Disease: A Prospective
Phase 1/2 Study. Zecca et al. Abstract #EP1387
|
E-Poster Session:
Stem Cell Transplantation - Clinical
|
Prognostic Biomarker
Testing And Treatment Selections In Patients With Chronic
Lymphocytic Leukemia Pre- And Post-Approval Of Novel Agents. Mato
et al. Abstract #EP712
|
E-Poster Session:
Chronic Lymphocytic Leukemia and Related Disorders -
Clinical
|
Application Of iwCLL
Guidelines For Response Assessment In The Treatment Of Patients
With Chronic Lymphocytic Leukemia In The Real-World: An Analysis
From The INFORMCLL™ Registry. Barrientos et al. Abstract
#PB1908
|
Publication Only
Abstract
Chronic Lymphocytic
Leukemia and Related Disorders – Clinical
|
Venetoclax in
CLL
|
Extrapolating
Progression Free Survival Curves In CLL Using Peripheral Blood MRD
Measurements From Venetoclax Trials. Alexiou et al.; Abstract
#EP708
|
E-Poster Session:
Chronic Lymphocytic Leukemia and Related Disorders –
Clinical
|
Efficacy of
Venetoclax in Patients with Relapsed/Refractory Chronic Lymphocytic
Leukemia: Primary Endpoint Analysis of the International Phase 3b
Trial (VENICE I). Kater et al.; Abstract #S156
|
Oral Session: CLL –
Targeted Therapy I
|
Impact of Venetoclax
Monotherapy on The Quality of Life of Patients with Relapsed or
Refractory Chronic Lymphocytic Leukemia: Results from VENICE II
Phase 3b Trial. Cochrane et al.; Abstract #EP701
|
E-Poster Session:
Chronic Lymphocytic Leukemia and Related Disorders –
Clinical
|
Phase 3b Study to
Evaluate Debulking Regimens Prior to Initiating Venetoclax Therapy
in Untreated Patients with Chronic Lymphocytic Leukemia. Sharman et
al.; Abstract #EP687
|
E-Poster Session:
Chronic Lymphocytic Leukemia and Related Disorders –
Clinical
|
Neutropenia Analysis
of Venetoclax Monotherapy in Patients with Relapsed or Refractory
Chronic Lymphocytic Leukemia: Pooled Data from VENICE-I and -II
Phase 3b Trials. Anderson et al.; Abstract #EP718
|
E-Poster Session:
Chronic Lymphocytic Leukemia and Related Disorders –
Clinical
|
Fixed-Duration
Venetoclax-Obinutuzumab for Previously Untreated Chronic
Lymphocytic Leukemia: Follow-Up of Efficacy and Safety Results from
the Multicenter, Open-Label, Randomized, Phase 3 CLL14 Trial.
Al-Sawaf et al.; Abstract #S155
|
Oral Session: CLL –
Targeted Therapy I
|
Characteristics and
Outcome of Patients with Chronic Lymphocytic Leukaemia and Partial
Response to Venetoclax-Obinutuzumab. Al-Sawaf et al.; Abstract
#EP699
|
E-Poster Session:
Chronic Lymphocytic Leukemia and Related Disorders –
Clinical
|
Impact of Premature
Venetoclax (VEN) Discontinuation/Interruption on Outcomes in
Relapsed/ Refractory (R/R) Chronic Lymphocytic Leukemia (CLL):
Results from the Phase 3 MURANO Study. Mato et al.; Abstract
#EP691
|
E-Poster Session:
Chronic Lymphocytic Leukemia And Related Disorders –
Clinical
|
Extended Follow-Up in
BIRC3- Mutated Relapsed/Refractory Chronic Lymphocytic Leukemia
(R/R CLL) Patients Treated With Fixed-Duration Venetoclax Plus
Rituximab: Subgroup Analyses of the MURANO Trial. Kater et al.;
Abstract #EP694
|
E-Poster Session:
Chronic Lymphocytic Leukemia And Related Disorders –
Clinical
|
Systematic Literature
Review and Network Meta-Analysis Comparing Therapies for
Treatment-Naïve Patients with Chronic Lymphocytic Leukemia. Sail et
al.; Abstract #EP725
|
E-Poster Session:
Chronic Lymphocytic Leukemia And Related Disorders –
Clinical
|
CLL2-GiVe, a
Prospective, Open-Label, Multicenter Phase-2 Trial of Obinutuzumab
(Ga101, G), Ibrutinib (I), Plus Venetoclax (Ve) in Untreated
Patients with CLL With 17p Deletion / Tp53 Mutation. Huber et al.;
Abstract #S157
|
Oral Session: CLL –
Targeted Therapy I
|
Kinetics of Response
in the Peripheral Blood Predicts Long Term Responses to Ibrutinib +
Venetoclax Treatment for Relapsed/Refractory CLL in the Bloodwise
TAP CLARITY trial. Rawstron et al.; Abstract #S164
|
Oral Session: CLL –
Targeted Therapy II
|
Venetoclax in
AML
|
Long-Term Follow Up:
Phase 1b/2 Study of Venetoclax Plus Low-Dose Cytarabine in
Previously Untreated Older Adults with Acute Myeloid Leukemia
Ineligible for Intensive Chemotherapy. Wei et al.; Abstract
#EP554
|
E-Poster Session:
Acute Myeloid Leukemia – Clinical
|
Timing of Response to
Venetoclax Combination Treatment in Older Patients with Acute
Myeloid Leukemia. Jonas et al.; Abstract #EP535
|
E-Poster Session:
Acute Myeloid Leukemia – Clinical
|
Real-World Data (RWD)
Cohort of Patients with Acute Myeloid Leukemia (AML) in the United
States from an Electronic Health Record (EHR)–Derived De-Identified
Database. Flahavan et al.; Abstract #EP600
|
E-Poster Session:
Acute Myeloid Leukemia – Clinical
|
Transfusion Burden on
Older Patients with Acute Myeloid Leukemia Receiving Low-Intensity
Treatments. Le Blanc et al.; Abstract #EP1739
|
E-Poster Session:
Quality of Life, Palliative & Supportive Care, Ethics and
Health Economics
|
Phase 1b/2 Study of
the IDH1-Mutant Inhibitor Ivosidenib with the BCL2 Inhibitor
Venetoclax +/- Azacitidine in IDH1-Mutated Hematologic
Malignancies. DiNardo et al.; Abstract #S143*
|
Oral Session: Acute
Myeloid Leukemia – Clinical
|
A Phase 3 Study of
Venetoclax Plus Low-Dose Cytarabine in Previously Untreated Older
Patients with Acute Myeloid Leukemia (VIALE-C): A 6-Month Update.
Wei et al.; Abstract #S136
|
Oral Session: AML
Randomized Trials
|
Treatment Patterns
and Outcomes of Newly Diagnosed Acute Myeloid Leukemia Patients
Receiving Venetoclax Combinations Vs Other Therapies: Results from
the AML Real World Evidence (ARC) Initiative. Talati et al.
Abstract #PB1831
|
Publication Only
Abstract
Acute Myeloid
Leukemia – Clinical
|
First-In-Human Study
of a TRAIL Receptor Agonist Fusion Protein, Eftozanermin Alfa, in
Patients With Relapsed/Refractory Acute Myeloid Leukemia and
Diffuse Large B-Cell Lymphoma. Jongen-Lavrencic et al. Abstract
#EP589
|
E-Poster Session:
Acute Myeloid Leukemia – Clinical
|
Venetoclax in
MDS
|
A Phase 1b Study
Evaluating the Safety and Efficacy of Venetoclax in Combination
with Azacitidine for the Treatment of Relapsed/Refractory
Myelodysplastic Syndrome. Zeidan et al.; Abstract #S188
|
Oral Session:
Myelodysplastic Syndromes – Clinical
|
The Prognostic Impact
of Cytogenetic Scores in Patients with Higher-Risk Myelodysplastic
Syndrome Treated with Venetoclax and Azacitidine in a Phase 1
Study. Garcia et al.; Abstract #EP795
|
E-Poster Session:
Myelodysplastic Syndromes – Clinical
|
Venetoclax in
ALL
|
Safety and Efficacy
of Venetoclax in Combination with Navitoclax in Adult and Pediatric
Relapsed/Refractory Acute Lymphoblastic Leukemia and Lymphoblastic
Lymphoma. Jabbour et al.; Abstract #S116
|
Oral Session:
Cellular, Antibody and Targeted Therapy
|
Venetoclax in
MM
|
Updated Results from
a Phase 1/2 Study of Venetoclax in Combination with Daratumumab and
Dexamethasone, +/- Bortezomib, in Patients with Relapsed/Refractory
Multiple Myeloma. Kaufman et al.; Abstract #EP940
|
E-Poster Session:
Myeloma and Other Monoclonal Gammopathies – Clinical
|
Updated Results from
BELLINI, a Phase 3 Study of Venetoclax or Placebo in
Combination With Bortezomib and Dexamethasone in
Relapsed/Refractory Multiple Myeloma. Kumar et al.; Abstract
#EP939
|
E-Poster Session:
Myeloma and Other Monoclonal Gammopathies – Clinical
|
Evaluation of Minimal
Residual Disease in Relapsed/Refractory Multiple Myeloma Patients
Treated with Venetoclax or Placebo in Combination with Bortezomib
and Dexamethasone: BELLINI Study Analyses. Moreau et al.; Abstract
#EP975
|
E-Poster Session:
Myeloma and Other Monoclonal Gammopathies – Clinical
|
|
|
The EHA 2020 Annual Congress abstracts are available at
www.ehaweb.org.
AbbVie will also present data from 17 accepted abstracts during
the virtual American Society of Clinical Oncology (ASCO) Annual
Meeting from May 29-31, 2020,
including studies of ibrutinib, venetoclax and veliparib.
About IMBRUVICA
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. 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 11 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 99 countries and has been used to
treat more than 195,000 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.
In early 2019, the National Comprehensive Cancer
Network® (NCCN®), a not-for-profit
alliance of 28 leading cancer centers devoted to patient care,
research, and education, recommends ibrutinib (IMBRUVICA) as a
preferred regimen for the initial treatment of CLL/SLL and it is
the only Category 1 treatment for treatment-naïve patients without
deletion 17p. In February 2020, the NCCN
Guidelines® were updated to elevate IMBRUVICA with
or without rituximab from other recommended regimens to a preferred
regimen for the treatment of relapsed/refractory MCL.
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.
IMPORTANT SAFETY INFORMATION
WARNINGS AND PRECAUTIONS
Hemorrhage: Fatal bleeding events have occurred in
patients who received 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) occurred in 4% of patients, with fatalities occurring
in 0.4% of 2,838 patients who received
IMBRUVICA® in 27 clinical trials. Bleeding events,
including bruising and petechiae, occurred in 39% of patients who
received 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. Across clinical trials, 3.1% of 2,838 patients who
received 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 21% of 1,476 patients who received
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: In 645 patients with B?cell malignancies
who received IMBRUVICA® as a single agent, Grade 3
or 4 neutropenia occurred in 23% of patients, Grade 3 or 4
thrombocytopenia in 8% and Grade 3 or 4 anemia in 3%, based on
laboratory measurements.
Monitor complete blood counts monthly.
Cardiac Arrhythmias: Fatal and serious cardiac
arrhythmias have occurred with IMBRUVICA®. 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 1,476 patients who received
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 occurred in 19% of 1,476
patients who received IMBRUVICA® in clinical
trials. Grade 3 or greater hypertension occurred in 8% of
patients. Based on data from 1,124 of these patients, the median
time to onset was 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%), occurred among the
1,476 patients who received 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®. 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 pregnant women of the potential risk to
a fetus. Advise females of reproductive potential to use effective
contraception during treatment with IMBRUVICA® and
for 1 month after the last dose. Advise males with female partners
of reproductive potential to use effective contraception during the
same time period.
ADVERSE REACTIONS
B-cell malignancies: The most common adverse
reactions (≥30%) in patients with B-cell malignancies (MCL,
CLL/SLL, WM and MZL) were thrombocytopenia (54.5%)*, diarrhea
(43.8%), fatigue (39.1%), musculoskeletal pain (38.8%), neutropenia
(38.6%)*, rash (35.8%), anemia (35.0%)*, and bruising (32.0%).
The most common Grade ≥ 3 adverse reactions (≥5%) in patients
with B-cell malignancies (MCL, CLL/SLL, WM and MZL) were
neutropenia (20.7%)*, thrombocytopenia (13.6%)*, pneumonia (8.2%),
and hypertension (8.0%).
Approximately 9% (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 recommended
IMBRUVICA® dose and monitor more frequently for
adverse reactions of IMBRUVICA®.
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.
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.
This indication is approved under accelerated approval based on
response rates. Continued approval for this indication may be
contingent upon verification and description of clinical benefit in
confirmatory trials
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 obinutuzumab is indicated for the
treatment of adult patients with previously untreated chronic
lymphocytic leukaemia (CLL).
Venclyxto in combination with rituximab is indicated for the
treatment of adult patients with 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
TLS, including fatal events, has occurred in patients with
previously treated CLL with high tumour 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 sepsis with fatal outcome have been
reported. Monitoring of any signs and symptoms of infection is
required. Suspected infections should receive prompt
treatment including antimicrobials and dose interruption or
reduction as appropriate.
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: moderate or strong
CYP3A inhibitors must be used, physicians should refer to the
VENCLYXTO summary of product characteristics (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 studies
with obinutuzumab or rituximab were neutropenia, diarrhoea, and
upper respiratory tract infection. In the monotherapy
studies, the most common adverse reactions were
neutropenia/neutrophil count decreased, diarrhoea, nausea, anaemia,
fatigue, and upper respiratory tract infection.
The most frequently occurring serious adverse reactions
(>=2%) in patients receiving venetoclax in combination with
obinutuzumab or rituximab were pneumonia, sepsis, febrile
neutropenia, and TLS. In the monotherapy studies, the most
frequently reported serious adverse reactions (>=2%) were
pneumonia and febrile neutropenia.
Discontinuations due to adverse reactions occurred in 16% of
patients treated with venetoclax in combination with obinutuzumab
or rituximab in the CLL14 and Murano studies respectively. In
the monotherapy studies with venetoclax, 11% of patients
discontinued due to adverse reactions.
Dosage reductions due to adverse reactions occurred in 21% of
patients treated with the combination of venetoclax and
obinutuzumab in CLL14 and in 15% of patients treated with the
combination of venetoclax and in Murano and in 14% of patients
treated with venetoclax in the monotherapy
studies. The most common adverse reaction that
led to dose interruptions was neutropenia.
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 https://www.ema.europa.eu/en/documents/product-information/venclyxto-epar-product-information_en.pdf.
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's mission is to discover and deliver innovative medicines
that solve serious health issues today and address the medical
challenges of tomorrow. We strive to have a remarkable impact on
people's lives across several key therapeutic areas: immunology,
oncology, neuroscience, eye care, virology, women's health and
gastroenterology, in addition to products and services across its
Allergan Aesthetics portfolio. For more information about AbbVie,
please visit us at www.abbvie.com. Follow @abbvie on
Twitter, Facebook, Instagram, YouTube and
LinkedIn.
Forward-Looking Statements
Some statements in this news release are, or may be considered,
forward-looking statements for purposes of the Private Securities
Litigation Reform Act of 1995. The words "believe," "expect,"
"anticipate," "project" and similar expressions, among others,
generally identify forward-looking statements. AbbVie cautions that
these forward-looking statements are subject to risks and
uncertainties that may cause actual results to differ materially
from those indicated in the forward-looking statements. Such risks
and uncertainties include, but are not limited to, competition from
other products, challenges to intellectual property, difficulties
inherent in the research and development process, adverse
litigation or government action, and changes to laws and
regulations applicable to our industry. Additional information
about the economic, competitive, governmental, technological and
other factors that may affect AbbVie's operations is set forth in
Item 1A, "Risk Factors," of AbbVie's 2019 Annual Report on Form
10-K, which has been filed with the Securities and Exchange
Commission. AbbVie undertakes no obligation to release publicly any
revisions to forward-looking statements as a result of subsequent
events or developments, except as required by law.
1 AbbVie Receives European Commission Approval of
VENCLYXTO® Combination Regimen for Patients with
Previously-Untreated Chronic Lymphocytic Leukemia. Published online
March 12, 2020.
https://news.abbvie.com/news/press-releases/abbvie-receives-european-commission-approval-venclyxto-combination-regimen-for-patients-with-previously-untreated-chronic-lymphocytic-leukemia.htm.
2 Genetics Home Reference. Isolated growth hormone
deficiency.
http://ghr.nlm.nih.gov/condition/isolated-growth-hormone-deficiency.
Accessed January 2020.
3 Turetsky, et al. Single cell imaging of Bruton's
Tyrosine Kinase using an irreversible inhibitor. Scientific
Reports. volume 4, Article number: 4782 (2014).
4 de Rooij MF, Kuil A, Geest CR, et al. The
clinically active BTK inhibitor PCI-32765 targets B-cell receptor-
and chemokine-controlled adhesion and migration in chronic
lymphocytic leukemia. Blood. 2012;119(11):2590-2594.
5 IMBRUVICA U.S. Prescribing Information, April 2020.
6 VENCLEXTA (venetoclax) [Package Insert]. North Chicago, IL.: AbbVie Inc.
7 Summary of Product Characteristics for VENCLYXTO
(venetoclax). Ludwigshafen, Germany: AbbVie Deutschland GmbH & Co.
KG.
+ Presentations will be made available on the on-demand
Virtual Congress platform as of Friday, June
12 at 08:30 CEST and will be
accessible until October 15,
2020.
* Venetoclax is indicated in AML and CLL
View original
content:http://www.prnewswire.com/news-releases/abbvie-data-at-eha-annual-congress-highlight-depth-and-breadth-of-transformative-blood-cancer-portfolio-301060034.html
SOURCE AbbVie