NORTH CHICAGO, Ill.,
June 11, 2021 /PRNewswire/
-- AbbVie (NYSE: ABBV) today announced results from a
four-year follow-up analysis of the Phase 3 CLL14 trial, which
showed that previously untreated patients with chronic lymphocytic
leukemia (CLL) with coexisting conditions who were treated with
VENCLYXTO®/VENCLEXTA® (venetoclax) plus
obinutuzumab continued to show longer progression-free survival
(PFS) and higher rates of undetectable minimal residual disease
(MRD) compared to patients receiving a standard of care
chemoimmunotherapy regimen of obinutuzumab and chlorambucil. The
data were presented for the first time today during the virtual
26th European Hematology Association (EHA) Annual
Congress (abstract #S146).
"The CLL14 trial results observed after four years of follow-up
with treatment of venetoclax plus obinutuzumab show that these
patients can experience long-lasting responses without disease
progression, years after stopping treatment," said Mohamed Zaki, M.D., Ph.D., vice president and
head, global oncology development, AbbVie.
After a median follow-up of more than four years (52.4 months),
patients treated with the VENCLYXTO/VENCLEXTA and obinutuzumab
combination (n=216) continued to demonstrate longer PFS compared to
patients on treatment with obinutuzumab and chlorambucil, the risk
of disease progression or death was reduced by 67 percent (n=216;
median not reached compared to 36.4 months; hazard ratio [HR] 0.33
[95% CI 0.25-0.45]); results are descriptive. At four years after
randomization, the PFS rate for patients treated with the
VENCLYXTO/VENCLEXTA-based combination was 74 percent compared to
35.4 percent for patients treated with obinutuzumab and
chlorambucil. The improvement in PFS was observed across all
clinical and biological risk groups, including patients with TP53
mutation, 17p deletion and unmutated IGHV status.1
Additionally, assessment of MRD in peripheral blood 30 months
after the end of treatment showed that 26.9 percent of patients
treated with the VENCLYXTO/VENCLEXTA-based combination still
had undetectable MRD (<10-4) compared to 3.2 percent
of patients in the obinutuzumab plus chlorambucil
arm.1 Undetectable MRD occurs when less than one
CLL cell per 10,000 lymphocytes can be detected in the blood or
bone marrow using sensitive analytical
No new safety signals were observed in the four-year follow-up
analysis.1 The most frequently
occurring serious adverse reactions (>=2%) in patients receiving
venetoclax in combination with obinutuzumab were pneumonia, sepsis,
febrile neutropenia, and TLS.3
"CLL is considered an incurable disease and becomes more
difficult to treat each time a patient experiences a relapse, so a
key treatment goal is to maintain remission for as long as
possible. The four- year results of the CLL14 study show that 74
percent of patients treated with fixed-duration
venetoclax-obinutuzumab remain without PFS event, more than three
years after treatment cessation," said Othman Al-Sawaf, M.D., lead
investigator of the CLL14 study, hematologist-oncologist at the
University Hospital Cologne in Germany, and study physician at the German CLL
Study Group. "This highlights how durable the remissions are after
12 treatment cycles in the vast majority of patients, suggesting
the venetoclax-obinutuzumab combination regimen as an effective
option for patients with previously untreated CLL."
CLL is a slow-growing form of leukemia, or blood cancer, in
which too many immature lymphocytes (a type of white blood cell)
are found predominantly in the blood and bone marrow. CLL is the
most common form of leukemia in the Western Hemisphere, accounting
for approximately one third of new leukemia diagnoses and nearly
95,000 new cases in Europe each
VENCLYXTO/VENCLEXTA 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.
About the CLL14 Phase 3
prospective, multicenter, open-label, randomized Phase 3 CLL14
trial, which was conducted in close collaboration with the German
CLL Study Group (DCLLSG), evaluated the efficacy and safety of a
combined regimen of VENCLYXTO/VENCLEXTA and obinutuzumab (n=216)
versus obinutuzumab and chlorambucil (n=216) in previously
untreated patients with CLL and coexisting medical conditions
(total Cumulative Illness Rating Scale [CIRS] score >6 or
creatinine clearance <70 mL/min). The therapies were
administered for a fixed duration of 12 months for
VENCLYXTO/VENCLEXTA in combination with six cycles of obinutuzumab.
The trial enrolled 432 patients, all of whom were previously
untreated according to the International Workshop on Chronic
Lymphocytic Leukemia (iwCLL) criteria. Efficacy was based on PFS as
assessed by an independent review committee.
Key secondary endpoints were rates of MRD in peripheral blood
and bone marrow, overall and complete response rates, MRD in
complete response in peripheral blood and bone marrow, and overall
The four-year, follow-up analysis showed an OS rate of 85.4%
with Ven-Obi versus 83.1% with chlorambucil in combination with
obinutuzumab (Obi-Clb; HR 0.85, 95% CI [0.54-1.35]; P=0.49).
In patients with CLL receiving combination therapy with
obinutuzumab, serious adverse reactions (ARs) were most often due
to febrile neutropenia and pneumonia (5 percent each). The most
common ARs (≥20 percent) of any grade were neutropenia (60
percent), diarrhea (28 percent), and fatigue (21 percent). Fatal
ARs that occurred in the absence of disease progression and with
onset within 28 days of the last study treatment were reported in 2
percent (4/212) of patients, most often from infection.
About VENCLYXTO® (venetoclax)
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. VENCLYXTO targets the BCL-2 protein and works to help
restore the process of apoptosis.
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. Venetoclax is approved in more than 80 countries,
including the U.S.
Indication and Important VENCLYXTO (venetoclax) EU Safety
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
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
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
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
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
Live vaccines should not be administered during treatment or
thereafter until B-cell recovery.
In CLL and AML CYP3A inhibitors may increase Venclyxto plasma
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
Co-administration of bile acid sequestrants with VENCLYXTO is
not recommended as this may reduce the absorption of VENCLYXTO.
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
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.
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
Venclyxto may cause embryo-fetal harm when administered to a
pregnant woman. Advise nursing women to discontinue breastfeeding
This is not a complete summary of all safety information. See
Venclyxto (venetoclax) 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 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
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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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1 Al-Sawaf O, et al.
Venetoclax-obinutuzumab for previously untreated chronic
lymphocytic leukemia: 4-year follow-up analysis of the randomized
CLL14 study. Presented at the European Hematology Association
Annual Meeting; June 11, 2021.
2 Hallek M, et al. Guidelines for
diagnosis, indications for treatment, response assessment and
supportive management of chronic lymphocytic
leukemia. Blood. 2018;131(25):2745-2760.
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Ludwigshafen, Germany: AbbVie Deutschland GmbH & Co.
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Accessed February 2020.
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6 World Health Organization. 2014
Review of Cancer Medicines on the WHO List of Essential Medicines.
Accessed January 2020.
7 VENCLEXTA (venetoclax) [Package
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8 Fischer K, et al. Venetoclax and
obinutuzumab in patients with CLL and coexisting conditions. N
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