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See what this means for patients with previously untreated CLL.
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Prescribing Information

Sponsored by AbbVie Inc. and Genentech, Inc.

VENCLEXTA + GAZYVA® (obinutuzumab) for 1L CLL treatment DEMONSTRATED DURABLE PFS
WITHOUT LONG-TERM TREATMENT1

• The VENCLEXTA + GAZYVA regimen (VEN+G) is designed to be completed after 12
months (twelve 28-day treatment cycles). In the VEN+G arm of the CLL14 trial,
GAZYVA was administered in Cycles 1-6 and VENCLEXTA was administered orally 400
mg/day from Cycle 3, Day 1, after the first two cycles of GAZYVA and the 5-week
VENCLEXTA dose ramp-up. In the GAZYVA + chlorambucil (GClb) arm of the CLL14
trial, GAZYVA was administered in Cycles 1-6. Chlorambucil was administered at
0.5 mg/kg orally on Day 1 and Day 15 of Cycles 1-121

In a randomized (1:1), multicenter, open-label, actively controlled, phase 3
trial (CLL14), VEN+G was studied against chlorambucil plus GAZYVA (GClb) in 432
patients with previously untreated CLL with comorbid medical conditions (total
CIRS score >6 or CLcr <70 mL/min). The primary endpoint was IRC-assessed
progression-free survival (PFS).1

67% reduction in risk of progression
or death vs GClb (HR=0.33;
95% CI: 0.22-0.51 [P<0.0001])1

• After a median follow-up of 28 months (range: 0-36 months), there were 29
events in the VEN+G arm (14 progressions and 15 deaths without disease
progression) compared with 79 in the GClb arm (71 progressions and 8 deaths
without progression).* Median PFS was not reached in either arm1

4-year post hoc analysis of INV-assessed PFS2† The post hoc analysis was not
tested for statistical significance. The rates shown for PFS are estimates and
can be unreliable due to a large number of patients censored at the tail end of
the curve.

• With a median follow-up of 52.4 months (range: 0-61.1 months), median PFS was
not reached for the VEN+G arm (95% CI: 57.3-NE) and was estimated to be 36.4
months (95% CI: 34.1-41.0) in the GClb arm (HR=0.33; 95% CI: 0.25-0.45) • Of the
61 events in the VEN+G arm, 26 were deaths without disease progression and 35
were disease progression. Of the 138 events in the GClb arm, 16 were deaths
without disease progression and 122 were disease progression*

A post hoc survival analysis was performed at the 4-year follow-up2†

• Overall survival (OS) data remained immature, and the median OS had not been
reached in either arm • There were 34 events in the VEN+G arm and 41 in the GClb
arm

- Rates of death were 16% in the VEN+G arm and 19% in the GClb arm (HR=0.85; 95%
CI: 0.54-1.35)

*Number of events based on earliest event of disease progression or deaths
without disease progression due to any cause.1 †Based on data as of clinical
data cutoff date of September 11, 2020.

Considering VENCLEXTA for your patients?
See additional efficacy data >

1L=first line; CLL=chronic lymphocytic leukemia; IRC=Independent Review
Committee; HR=hazard ratio; CI=confidence interval; CLcr=creatinine clearance;
INV=investigator; CIRS=Cumulative Illness Rating Scale; NE=not estimable.

Indication & Important Safety Information Indication

• VENCLEXTA is indicated for the treatment of adult patients with chronic
lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).

Important Safety Information Contraindication

• Concomitant use of VENCLEXTA with strong CYP3A inhibitors at initiation and
during ramp-up phase is contraindicated in patients with CLL/SLL due to the
potential for increased risk of tumor lysis syndrome (TLS).

Tumor Lysis Syndrome

• Tumor lysis syndrome, including fatal events and renal failure requiring
dialysis, has occurred in patients treated with VENCLEXTA. • VENCLEXTA can cause
rapid reduction in tumor and thus poses a risk for TLS at initiation and during
the ramp-up phase in all patients, and during reinitiation after dosage
interruption in patients with CLL/SLL. Changes in blood chemistries consistent
with TLS that require prompt management can occur as early as 6 to 8 hours
following the first dose of VENCLEXTA and at each dose increase. TLS, including
fatal cases, has been reported after a single 20 mg dose. • In patients with
CLL/SLL who followed the current (5 week) dose ramp-up and the TLS prophylaxis
and monitoring measures, the rate of TLS was 2% in the VENCLEXTA CLL/SLL
monotherapy trials. The rate of TLS remained consistent with VENCLEXTA in
combination with obinutuzumab or rituximab. With a 2- to 3-week dose ramp-up and
higher starting dose in patients with CLL/SLL, the TLS rate was 13% and included
deaths and renal failure. • The risk of TLS is a continuum based on multiple
factors, particularly reduced renal function, tumor burden, and type of
malignancy. Splenomegaly may also increase the risk of TLS in patients with
CLL/SLL. • Assess all patients for risk and provide appropriate prophylaxis for
TLS, including hydration and anti-hyperuricemics. Monitor blood chemistries and
manage abnormalities promptly. Employ more intensive measures (IV hydration,
frequent monitoring, hospitalization) as overall risk increases. Interrupt
dosing if needed; when restarting VENCLEXTA follow dose modification guidance in
the Prescribing Information. • Concomitant use of VENCLEXTA with P-gp inhibitors
or strong or moderate CYP3A inhibitors increases venetoclax exposure, which may
increase the risk of TLS at initiation and during the ramp-up phase, and
requires VENCLEXTA dose reduction.

Important Safety Information (continued) Neutropenia

• In patients with CLL, Grade 3 or 4 neutropenia developed in 63% to 64% of
patients and Grade 4 neutropenia developed in 31% to 33% of patients when
treated with VENCLEXTA in combination and monotherapy studies. Febrile
neutropenia occurred in 4% to 6% of patients. • Monitor complete blood counts.
Interrupt dosing for severe neutropenia and resume at same or reduced dose.
Consider supportive measures including antimicrobials and growth factors (e.g.,
G-CSF).

Infections

• Fatal and serious infections such as pneumonia and sepsis have occurred in
patients treated with VENCLEXTA. Monitor patients for signs and symptoms of
infection and treat promptly. Withhold VENCLEXTA for Grade 3 and 4 infection
until resolution and resume at same or reduced dose.

Immunization

• Do not administer live attenuated vaccines prior to, during, or after
treatment with VENCLEXTA until B-cell recovery occurs. Advise patients that
vaccinations may be less effective.

Embryo-Fetal Toxicity

• VENCLEXTA may cause embryo-fetal harm when administered to a pregnant woman.
Advise females of reproductive potential to use effective contraception during
treatment and for at least 30 days after the last dose.

Increased Mortality in Patients with Multiple Myeloma when VENCLEXTA is Added to
Bortezomib and Dexamethasone

• In a randomized trial (BELLINI; NCT02755597) in patients with relapsed or
refractory multiple myeloma, the addition of VENCLEXTA to bortezomib plus
dexamethasone, a use for which VENCLEXTA is not indicated, resulted in increased
mortality. Treatment of patients with multiple myeloma with VENCLEXTA in
combination with bortezomib plus dexamethasone is not recommended outside of
controlled clinical trials.

Adverse Reactions

• In patients with CLL receiving combination therapy with obinutuzumab, serious
adverse reactions were most often due to febrile neutropenia and pneumonia (5%
each). The most common adverse reactions (≥20%) of any grade were neutropenia
(60%), diarrhea (28%), and fatigue (21%). Fatal adverse reactions that occurred
in the absence of disease progression and with onset within 28 days of the last
study treatment were reported in 2% (4/212) of patients, most often from
infection. • In patients with CLL receiving combination therapy with rituximab,
the most frequent serious adverse reaction (≥5%) was pneumonia (9%). The most
common adverse reactions (≥20%) of any grade were neutropenia (65%), diarrhea
(40%), upper respiratory tract infection (39%), fatigue (22%), and nausea (21%).
Fatal adverse reactions that occurred in the absence of disease progression and
within 30 days of the last VENCLEXTA treatment and/or 90 days of the last
rituximab were reported in 2% (4/194) of patients. • In patients with CLL/SLL
receiving monotherapy, the most frequent serious adverse reactions (≥5%) were
pneumonia (9%), febrile neutropenia (5%), and sepsis (5%). The most common
adverse reactions (≥20%) of any grade were neutropenia (50%), diarrhea (43%),
nausea (42%), upper respiratory tract infection (36%), anemia (33%), fatigue
(32%), thrombocytopenia (29%), musculoskeletal pain (29%), edema (22%), and
cough (22%). Fatal adverse reactions that occurred in the absence of disease
progression and within 30 days of venetoclax treatment were reported in 2% of
patients in the VENCLEXTA monotherapy studies, most often (2 patients) from
septic shock.

Drug Interactions

• Concomitant use with a P-gp inhibitor or a strong or moderate CYP3A inhibitor
increases VENCLEXTA exposure, which may increase VENCLEXTA toxicities, including
the risk of TLS. Consider alternative medications or adjust VENCLEXTA dosage and
monitor more frequently for adverse reactions. Resume the VENCLEXTA dosage that
was used prior to concomitant use of a P-gp inhibitor or a strong or moderate
CYP3A inhibitor 2 to 3 days after discontinuation of the inhibitor. • Patients
should avoid grapefruit products, Seville oranges, and starfruit during
treatment as they contain inhibitors of CYP3A. • Avoid concomitant use of strong
or moderate CYP3A inducers. • Monitor international normalized ratio (INR) more
frequently in patients receiving warfarin. • Avoid concomitant use of VENCLEXTA
with a P-gp substrate. If concomitant use is unavoidable, separate dosing of the
P-gp substrate at least 6 hours before VENCLEXTA.

Lactation

• Advise women not to breastfeed during treatment with VENCLEXTA and for 1 week
after the last dose.

Females and Males of Reproductive Potential

• Advise females of reproductive potential to use effective contraception during
treatment with VENCLEXTA and for at least 30 days after the last dose. • Based
on findings in animals, VENCLEXTA may impair male fertility.

Hepatic Impairment

• Reduce the dose of VENCLEXTA for patients with severe hepatic impairment
(Child-Pugh C); monitor these patients more frequently for adverse reactions. No
dose adjustment is recommended for patients with mild (Child-Pugh A) or moderate
(Child-Pugh B) hepatic impairment.

Please see full Prescribing Information.

VENCLEXTA® and its design are registered trademarks of AbbVie Inc. GAZYVA® is a
registered trademark of Genentech, Inc. References: 1. VENCLEXTA Prescribing
Information. 2. Data on file, AbbVie Inc. ABVRRTI72219.



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