R/R CLL
NEW
VEN+R DEMONSTRATED DURABLE
IRC-ASSESSED PFS WITH ~24 MONTHS
OF TREATMENT 1,2
81 %
reduction in risk of progression or death vs
BR (HR=0.19; 95% CI: 0.13–0.28 [P<0.0001] ‡ )
• After a median follow-up of 23.4 months (range: 0–37.4+ months),
there were 35 events in the VEN+R arm (26 progression and 9 death
events) compared with 106 events in the BR arm (91 progression
and 15 death events)
• The median PFS was not reached with VEN+R vs 18.1 months
(95% CI: 15.8–22.3) with BR
83 %
• The estimated 24-month PFS was 83% (95% CI: 77–89)
for VEN+R vs 39% (95% CI: 31–48) for BR §
48-MONTH POST HOC ANALYSIS
OF INV-ASSESSED PFS AFTER STOPPING
TREATMENT AT ~24 MONTHS 3ll
In patients who have been off treatment for ~2 years:
• Median PFS was estimated to be 52.3 months ¶ (95% CI: 47.9–NE)
with VEN+R and was 17.1 months (95% CI: 15.7–22.1) for BR
(HR=0.19; 95% CI: 0.14–0.25)
57 %
• 48-month PFS estimates were 57% (95% CI: 49–65) in
VEN+R, compared with 5% (95% CI: 0–9) in BR
• The median follow-up was 47.9 months (range: 0–60.1 months), and
there were 78 events in the VEN+R arm and 160 events in the BR arm
• This analysis was not tested for statistical signifi cance
• Study design: MURANO was a randomized, multicenter,
open-label phase 3 study that evaluated the effi cacy and safety of
VENCLEXTA in combination with rituximab (VEN+R) versus BR in
patients with CLL who had received at least one line of prior
therapy. The primary endpoint was PFS
HR estimate is based on Cox proportional hazards model stratified by 17p deletion, risk status, and geographic region; P value is based on log-rank test stratified by the
same factors.
Estimated 24-month PFS rates were not prespecified and not tested for statistical significance.
ll
2-year data update based on data as of clinical cutoff date of May 8, 2019.
¶
Median PFS for VEN+R exceeds median follow-up.
IRC=independent review committee; PFS=progression-free survival; BR=bendamustine + rituximab; CI=confidence interval; HR=hazard ratio; INV=investigator;
NE=not estimable.
‡
§
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%).
• 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%), cough (22%), and
nausea (21%).
• 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%).
Drug Interactions
• Concomitant use with a strong or moderate CYP3A inhibitor or a P-gp inhibitor
increases VENCLEXTA exposure, which may increase VENCLEXTA toxicities,
including the risk of TLS. Adjust VENCLEXTA dosage and closely monitor
patients for signs of VENCLEXTA toxicities. Resume the VENCLEXTA dosage
that was used prior to concomitant use of a strong or moderate CYP3A
inhibitor or a P-gp inhibitor 2 to 3 days after discontinuation of the inhibitor.
Please see Brief Summary of full Prescribing Information on
the following pages.
US-VENC-190294/September 2019
Printed in USA
• 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.
• 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.
• Monitor international normalized ratio (INR) closely in patients receiving warfarin.
Lactation
• Advise nursing women to discontinue breastfeeding during treatment
with VENCLEXTA.
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 fi ndings in animals, male fertility may be compromised by
treatment with VENCLEXTA.
Hepatic Impairment
• Reduce the dose of VENCLEXTA for patients with severe hepatic impairment
(Child-Pugh C); monitor these patients more closely for signs of toxicity. No
dose adjustment is recommended for patients with mild (Child-Pugh A) or
moderate (Child-Pugh B) hepatic impairment.
References: 1. VENCLEXTA Prescribing Information. 2. Data on file, AbbVie Inc.
ABVRRTI66340. 3. Data on file, AbbVie Inc. ABVRRTI69128.
VENCLEXTA ® is a registered trademark of AbbVie Inc.
GAZYVA ® is a registered trademark of Genentech, Inc.