NORTH CHICAGO, Ill.,
June 12, 2021 /PRNewswire/ -- AbbVie
(NYSE: ABBV) today announced new data from the Phase 3 GLOW study
comparing the efficacy and safety of the combination of
IMBRUVICA® (ibrutinib) plus
VENCLEXTA®/VENCLYXTO® (venetoclax) (I+V)
versus chlorambucil plus obinutuzumab (C+O) for first-line
treatment in patients with chronic lymphocytic leukemia (CLL) or
small lymphocytic lymphoma (SLL) who had active disease requiring
treatment per the International Workshop on CLL (iwCLL) criteria.
The study met its primary endpoint of superior progression-free
survival (PFS) as assessed by an independent review committee (IRC)
with a HR 0.216 (95% CI, 0.131-0.357; p < 0.0001), demonstrating
a reduction in the risk of disease progression or death for I+V of
approximately 78% compared to C+O. I+V is the first all-oral,
once-daily, chemotherapy-free, fixed-duration investigational
combination. Results of the study will be presented at the European
Hematology Association (EHA) 2021 Virtual Congress (Abstract
#LB1902) during late-breaking abstract session on June 12 from
4:00-5:30 p.m. CEST.
The PFS benefit with I+V was consistent across pre-specified
subgroups, including patients 65 years and older and those with
comorbidities (CIRS >6). The median PFS for C+O was 21 months
while the median PFS for I+V had not been reached at the time of
analysis. The safety profile of I+V was generally consistent with
the safety profile of the single agents and tolerability profiles
were consistent with CLL treatment in the enrolled patient
population.
"With CLL being one of the most common types of blood cancer,
the expansion of research into additional treatment options for
patients is an important clinical undertaking," said Arnon Kater, M.D., Ph.D., deputy head of
hematology, University of Amsterdam Faculty of Medicine. "The
progression-free survival findings of ibrutinib and venetoclax in
the GLOW study are promising and show the potential to become an
additional treatment option for people living with CLL."
Secondary endpoints included rates of undetectable minimal
residual disease (uMRD), complete response rate (CR) and overall
response rate (ORR). The rate of uMRD in the bone marrow as
assessed by next generation sequencing was significantly higher for
patients treated with I+V compared to those treated with C+O
(p<0.0001). Three months after the completion of treatment uMRD
was observed in 51.9% and 17.1%, respectively. Peripheral blood
(PB) uMRD persisted 12 months after end of treatment in 49% with
I+V and 12% with C+O. The CR rate was also significantly higher
with I+V vs. C+O (38.7% vs. 11.4%) (p < 0.0001). The ORR was not
significantly different between I+V and C+O treated groups. Time to
subsequent therapy was longer for I+V (HR 0.143, 95% CI
0.05-0.41).
"We are encouraged by these results, which further support the
efficacy of these two well-established therapies,"
said Mohamed Zaki, M.D., Ph.D., vice president and head,
global oncology development, AbbVie. "We remain steadfast in our
commitment to continue the research and development of this
combination as a potential treatment for CLL with the ultimate goal
to put patients into remission with a fixed-duration, oral
therapy."
The safety profile of I+V was generally consistent with the
safety profile of the single agents and tolerability profiles were
consistent with CLL treatment in the enrolled patient population.
Most common grade ≥3 treatment-emergent adverse events (AEs) were
neutropenia (34.9%), infections (17%), and diarrhea (10.4%) for
I+V; neutropenia (49.5%), infections (11.4%), and thrombocytopenia
(20%) for C+O. At time of analysis, overall survival was immature;
there were eleven deaths in the fixed-duration I+V arm and twelve
in the C+O arm. Deaths during treatment occurred in seven patients
on I+V and two patients on C+O.
Results from the ongoing Phase 2 CAPTIVATE study, assessing the
I+V combination for first-line treatment of patients with CLL or
SLL (PCYC-1142), were presented at the 2021 American Society of
Clinical Oncology Annual Meeting (Abstract #7501) and the EHA 2021
Virtual Congress.
About CLL
CLL is one of the two most common forms of leukemia in adults and
is a type of cancer that can develop from cells in the bone marrow
that later mature into certain white blood cells (called
lymphocytes). While these cancer cells start in the bone
marrow, they later spread into the blood. There are approximately
195,129 people with CLL living in the
United States with more than 21,000 newly diagnosed patients
in 2021.1,2 CLL is predominately a disease of the
elderly, with a median age at diagnosis of 70 years and is more
common among men than women.3
About the GLOW Study
The GLOW study is a randomized, open label Phase 3 trial comparing
progression-free survival in patients treated with either I+V or
C+O as assessed by an Independent Review Committee. It enrolled
patients (pts) aged ≥65 years or 18-64 years with cumulative
illness rating scale score >6 or creatinine clearance <70
mL/min who had active disease requiring treatment per the
International Workshop on CLL (iwCLL) criteria. Patients with
del(17p) or known TP53 mutations were excluded. There
were 211 patients randomly assigned in a 1:1 ratio to receive
either I+V (106) and or C+O (105) and the median age was 71 years.
Patients assigned to I+V received treatment for 15 cycles (1 cycle
is 28 days), starting with three cycles of ibrutinib monotherapy
lead-in followed by the combination of I+V for 12 cycles. Patients
assigned to C+O were treated for six cycles.
About IMBRUVICA® (Ibrutinib)
IMBRUVICA® (ibrutinib) is a once-daily,
first-in-class BTK inhibitor that is administered orally, and is
jointly developed and commercialized by Pharmacyclics, LLC, an
AbbVie Company, and Janssen Biotech, Inc. (Janssen). 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.4,5 By blocking BTK,
IMBRUVICA may help move abnormal B cells out of their nourishing
environments in the lymph nodes, bone marrow, and other
organs.6
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
macroglobulinemia; 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.7
IMBRUVICA is now approved in more than 100 countries and
has been used to treat more than 230,000 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.
Since 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 has Category 1 treatment status
for treatment-naïve patients without deletion 17p. Since January
2020, the NCCN Guidelines® have categorized IMBRUVICA
with or without rituximab as a preferred regimen for the treatment
of relapsed/refractory MCL. As of September 2020, the NCCN
guidelines were updated to reflect IMBRUVICA with or without
rituximab as the only Category 1 preferred regimen for both
untreated and previously treated WM patients.
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.
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. VENCLXEXTA/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
cancers. Venetoclax is approved in more than 80 countries,
including the U.S.
IMPORTANT SAFETY INFORMATION
US IMBRUVICA® Important Side Effect
Information7
Before taking IMBRUVICA®, tell your healthcare
provider about all of your medical conditions, including if
you:
- have had recent surgery or plan to have surgery. Your
healthcare provider may stop IMBRUVICA® for any planned
medical, surgical, or dental procedure.
- have bleeding problems.
- have or had heart rhythm problems, smoke, or have a medical
condition that increases your risk of heart disease, such as high
blood pressure, high cholesterol, or diabetes.
- have an infection.
- have liver problems.
- are pregnant or plan to become pregnant.
IMBRUVICA® can harm your unborn baby. If you are able to
become pregnant, your healthcare provider will do a pregnancy test
before starting treatment with IMBRUVICA®. Tell your
healthcare provider if you are pregnant or think you may be
pregnant during treatment with IMBRUVICA®.
-
- Females who are able to become pregnant should use
effective birth control (contraception) during treatment with
IMBRUVICA® and for 1 month after the last dose.
- Males with female partners who are able to become
pregnant should use effective birth control, such as condoms,
during treatment with IMBRUVICA® and for 1 month after
the last dose.
- are breastfeeding or plan to breastfeed. Do not breastfeed
during treatment with IMBRUVICA® and for 1 week after
the last dose.
Tell your healthcare provider about all the medicines you
take, including prescription and over-the-counter medicines,
vitamins, and herbal supplements. Taking IMBRUVICA® with
certain other medicines may affect how IMBRUVICA® works
and can cause side effects.
How should I take IMBRUVICA®?
- Take IMBRUVICA® exactly as your healthcare provider
tells you to take it.
- Take IMBRUVICA® 1 time a day.
- Swallow IMBRUVICA® capsules or tablets whole with a
glass of water.
- Do not open, break or chew IMBRUVICA® capsules.
- Do not cut, crush or chew IMBRUVICA® tablets.
- Take IMBRUVICA® at about the same time each
day.
- If you miss a dose of IMBRUVICA® take it as soon as
you remember on the same day. Take your next dose of
IMBRUVICA® at your regular time on the next day. Do not
take extra doses of IMBRUVICA® to make up for a missed
dose.
- If you take too much IMBRUVICA® call your healthcare
provider or go to the nearest hospital emergency room right
away.
What should I avoid while taking
IMBRUVICA®?
- You should not drink grapefruit juice, eat grapefruit, or
eat Seville oranges (often used in marmalades) during treatment
with IMBRUVICA®. These products may increase the amount
of IMBRUVICA® in your blood.
What are the possible side effects of
IMBRUVICA®?
IMBRUVICA® may cause serious side effects,
including:
- Bleeding problems (hemorrhage) are common during
treatment with IMBRUVICA®, and can also be serious and
may lead to death. Your risk of bleeding may increase if you are
also taking a blood thinner medicine. Tell your healthcare provider
if you have any signs of bleeding, including: blood in your stools
or black stools (looks like tar), pink or brown urine, unexpected
bleeding, or bleeding that is severe or that you cannot control,
vomit blood or vomit looks like coffee grounds, cough up blood or
blood clots, increased bruising, dizziness, weakness, confusion,
change in your speech, or a headache that lasts a long time or
severe headache.
- Infections can happen during treatment with
IMBRUVICA®. These infections can be serious and may lead
to death. Tell your healthcare provider right away if you have
fever, chills, weakness, confusion, or other signs or symptoms of
an infection during treatment with IMBRUVICA®.
- Decrease in blood cell counts. Decreased blood counts
(white blood cells, platelets, and red blood cells) are common with
IMBRUVICA®, but can also be severe. Your healthcare
provider should do monthly blood tests to check your blood
counts.
- Heart problems. Serious heart rhythm problems
(ventricular arrhythmias, atrial fibrillation, and atrial flutter),
heart failure, and death have happened in people treated with
IMBRUVICA®, especially in people who have an increased
risk for heart disease, have an infection, or who have had heart
rhythm problems in the past. Tell your healthcare provider if you
get any symptoms of heart problems, such as feeling as if your
heart is beating fast and irregular, lightheadedness, dizziness,
shortness of breath, swelling of the feet, ankles, or legs, chest
discomfort, or you faint. If you develop any of these symptoms,
your healthcare provider may do a test to check your heart (ECG)
and may change your IMBRUVICA® dose.
- High blood pressure (hypertension). New or worsening
high blood pressure has happened in people treated with
IMBRUVICA®. Your healthcare provider may start you on
blood pressure medicine or change current medicines to treat your
blood pressure.
- Second primary cancers. New cancers have happened during
treatment with IMBRUVICA®, including cancers of the skin
or other organs.
- Tumor lysis syndrome (TLS). TLS is caused by the fast
breakdown of cancer cells. TLS can cause kidney failure and the
need for dialysis treatment, abnormal heart rhythm, seizure, and
sometimes death. Your healthcare provider may do blood tests to
check you for TLS.
The most common side effects of IMBRUVICA® in
adults with B-cell malignancies (MCL, CLL/SLL, WM and MZL)
include:
- diarrhea
- tiredness
- muscle and bone pain
- rash
- bruising
The most common side effects of IMBRUVICA® in
adults with cGVHD include:
- tiredness
- bruising
- diarrhea
- mouth sores (stomatitis)
- muscle spasms
- nausea
- pneumonia
Diarrhea is a common side effect in people who take
IMBRUVICA®. Drink plenty of fluids during treatment with
IMBRUVICA® to help reduce your risk of losing too much
fluid (dehydration) due to diarrhea. Tell your healthcare provider
if you have diarrhea that does not go away.
These are not all the possible side effects of
IMBRUVICA®. Call your doctor for medical advice about
side effects. You may report side effects to FDA at
1-800-FDA-1088.
General information about the safe and effective use of
IMBRUVICA®
Medicines are sometimes prescribed for purposes other than those
listed in a Patient Information leaflet. Do not use
IMBRUVICA® for a condition for which it was not
prescribed. Do not give IMBRUVICA® to other people, even
if they have the same symptoms that you have. It may harm them. You
can ask your pharmacist or healthcare provider for information
about IMBRUVICA® that is written for health
professionals.
Please click here for full Prescribing Information.
Uses of VENCLEXTA® (venetoclax) in US
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.
It is not known if VENCLEXTA is safe and effective in
children.
Important VENCLEXTA® (venetoclax) US Safety
Information
US VENCLEXTA® Important Safety
Information8
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. When
restarting VENCLEXTA after stopping for 1 week or longer, your
healthcare provider may again check for your risk of TLS and
change your dose.
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 and for 1 week after the last dose.
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 and may pause
dosing.
- 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 nausea; diarrhea; low platelet count;
constipation; low white blood cell count; fever with low white
blood cell count; tiredness; vomiting; swelling of arms, legs,
hands, or feet; fever; infection in lungs; shortness of breath;
bleeding; low red blood cell count; rash; stomach (abdominal) pain;
infection in your blood; muscle and joint pain; dizziness; cough;
sore throat; and low blood pressure.
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. Call your doctor for medical advice about side
effects.
You are encouraged to report side effects of
prescription drug to the FDA. Visit www.fda.gov/medwatch
or call 1-800-FDA-1088.
If you cannot afford your medication, contact
genentech-access.com/patient/brands/venclexta for
assistance.
The full U.S. prescribing information, including Medication
Guide, for VENCLEXTA® can be
found here.
Indications and Important
VENCLYXTO® (venetoclax) EU Safety
Information9
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.
Venclyxto in combination with a hypomethylating agent is
indicated for the treatment of adult patients with newly diagnosed
acute myeloid leukaemia (AML) who are ineligible for intensive
chemotherapy.
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 tumour lysis syndrome (TLS). Concomitant use of
preparations containing St. John's wort as Venclyxto
efficacy may be reduced.
Special Warnings & Precautions for Use
Tumour Lysis syndrome, including fatal events, has occurred in
patients when treated with Venclyxto. For CLL and AML, please refer
to the indication-specific recommendations for prevention of TLS in
the Venclyxto summary of product characteristic (SmPC).
Patients should be assessed for risk and should receive
appropriate prophylaxis, monitoring, and management for
TLS. The risk of TLS is a continuum based on multiple factors,
including comorbidities. Venclyxto poses a risk for TLS at
initiation and during the 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.
Neutropenia (grade 3 or 4) has been reported. Complete blood
counts should be monitored throughout the treatment
period.
In patients with AML, neutropenia (grade 3 or 4) is common
before starting treatment. The neutrophil counts can worsen with
Venetoclax in combination with a hypomethylating agent. Neutropenia
can recur with subsequent cycles of therapy. Dose modification and
interruptions for cytopenias are dependent on remission status.
For CLL and AML, please refer to the indication-specific
recommendations for dose modifications for toxicities in the
Venclyxto SmPC.
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
In CLL and AML CYP3A inhibitors may increase Venclyxto plasma
concentrations.
In CLL, 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, please refer to the recommendations for
dose modifications in the Venclyxto SmPC.
In AML, please refer to the AML-specific recommendation for dose
modifications for potential interactions with CYP3A inhibitors, in
the Venclyxto SmPC.
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
CLL
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, in 15% of patients treated with the
combination of venetoclax and rituximab 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.
AML
The most commonly occurring adverse reactions (>=20%) of any
grade in patients receiving venetoclax in combination with
azacitidine or decitabine in the VIALE-A and M14-358, respectively,
were thrombocytopenia, neutropenia, febrile neutropenia, nausea,
diarrhoea, vomiting, anaemia, fatigue, pneumonia, hypokalaemia, and
decreased appetite, haemorrhage, dizziness/syncope, hypotension,
headache, abdominal pain, and anaemia.
The most frequently reported serious adverse reactions (≥5%) in
patients receiving venetoclax in combination with azacitidine were
febrile neutropenia, pneumonia, sepsis and haemorrhage. In M14-358,
the most frequently reported serious adverse reactions (≥5%) were
febrile neutropenia, pneumonia, bacteraemia and sepsis.
Discontinuations due to adverse reactions occurred in 24% of
patients treated with venetoclax in combination with azacitidine in
the VIALE-A study, and 26% of patients treated with venetoclax in
combination with decitabine in the M14-358 study, respectively.
Dosage reductions due to adverse reactions occurred in 2% of
patients in VIALE-A, and in 6 % of patients in M14-358. Venetoclax
dose interruptions due to adverse reactions occurred in 72% and 65
% of patients, respectively. The most common adverse reaction that
led to dose interruption (>10%) of Venetoclax in VIALE-A, were
febrile neutropenia, neutropenia, pneumonia, and
thrombocytopenia. The most common adverse reactions that led
to dose interruption (≥5%) of venetoclax in M14-358 were febrile
neutropenia, neutropenia/neutrophil count decreased, pneumonia,
platelet count decreased, and white blood cell count decreased.
Special Populations
Patients with reduced renal function (CrCl <80 mL/min) may
require more intensive prophylaxis and monitoring to reduce the
risk of TLS at initiation and during the dose-titration
phase. 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 are committed to transforming standards of care for
multiple blood cancers while advancing a dynamic pipeline of
investigational therapies across a range of cancer types. Our
dedicated and experienced team joins forces with innovative
partners to accelerate the delivery of potentially breakthrough
medicines. We are evaluating more than 20 investigational medicines
in over 300 clinical trials across some of the world's most
widespread and debilitating cancers. As we work to have a
remarkable impact on people's lives, we are committed to exploring
solutions to help patients obtain access to our cancer medicines.
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, failure to
realize the expected benefits from AbbVie's acquisition of Allergan
plc ("Allergan"), failure to promptly and effectively integrate
Allergan's businesses, competition from other products, challenges
to intellectual property, difficulties inherent in the research and
development process, adverse litigation or government action,
changes to laws and regulations applicable to our industry and the
impact of public health outbreaks, epidemics or pandemics, such as
COVID-19. 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 2020 Annual Report on Form 10-K, which has been filed with
the Securities and Exchange Commission, as updated by its
subsequent Quarterly Reports on Form 10-Q. 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.
References
1 IMS Database [Data on File].
2 National Cancer Institute. Cancer Stat Facts:
Leukemia - Chronic Lymphocytic Leukemia
(CLL). https://seer.cancer.gov/statfacts/html/clyl.html.
Accessed May 2021.
3 Shanafelt, et al. Age at Diagnosis and the
Utility of Prognostic Testing in Patients with Chronic Lymphocytic
Leukemia (CLL). Cancer. 2010; 116(20): 4777–4787.
4 Genetics Home Reference. Isolated growth hormone
deficiency.
http://ghr.nlm.nih.gov/condition/isolated-growth-hormone-deficiency.
Accessed November 2020.
5 Turetsky, et al. Single cell imaging of Bruton's
Tyrosine Kinase using an irreversible inhibitor. Scientific
Reports. volume 4, Article number: 4782 (2014)
6 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.
7 IMBRUVICA U.S. Prescribing Information.
8 VENCLEXTA (venetoclax) [Package
Insert]. North Chicago, IL.: AbbVie Inc.
9 Summary of Product Characteristics for VENCLYXTO
(venetoclax). Ludwigshafen, Germany: AbbVie Deutschland GmbH & Co.
KG.
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