ASH Clinical News Focus on Myeloid Malignancies | Page 17
VENCLEXTA™ is an oral BCL-2 inhibitor approved for the treatment of patients with chronic lymphocytic
leukemia (CLL) with 17p deletion, as detected by an FDA-approved test, who have received at least one
prior therapy.
This indication is approved under accelerated approval based on overall resp onse rate. Continued
approval for this indication may be contingent upon verification and description of clinical benefit in
a confirmatory trial.
patients achieved over 80% ORR—including
complete remissions
• Results per independent review committee (IRC) of
an open-label, single-arm, multicenter clinical trial of
106 previously treated CLL patients with 17p
deletion who had received at least one prior therapy
• Median number of prior therapies was 2.5 (range:
1-10) and median time on treatment at time of
evaluation was 12.1 months (range: 0 to 21.5 months)
• Efficacy was evaluated by ORR as assessed by
IRC using the International Workshop for Chronic
Lymphocytic Leukemia (iwCLL) and National Cancer
Institute–sponsored Working Group (NCI-WG)
guidelines
• 17p deletion was confirmed in peripheral blood
specimens from patients
• Patients received VENCLEXTA via a weekly ramp-up
schedule starting at 20 mg and ramping to 50 mg,
100 mg, 200 mg to 400 mg once daily until
disease progression or unacceptable toxicity
ORR=overall response rate (CR+CRi+nPR+PR);
CR=complete remission; CRi=CR with incomplete
marrow recovery; nPR=nodular PR; PR=partial
remission.
VENCLEXTA: ORR in an open-label,
single-arm, multicenter clinical trial
7.5% (n=8)
80 5.7% (n=6)
1.9% (n=2)
2.8% (n=3)
60 69.8% (n=74)
COMPLETE
REMISSION
(CR + CRi)
CR
40
CRi
nPR
20
PR
0
Previously treated CLL with 17p deletion (N=106)
• Median time to first response was 0.8 months (range: 0.1 to 8.1 months)
• Median duration of response has not yet been reached with approximately
12 months of follow-up; range is 2.9 to 19+ months
to a pregnant woman. Advise females of reproductive potential
to avoid pregnancy during treatment.
Adverse Reactions
• Serious adverse reactions were reported in 43.8% of patients. The
most frequent serious adverse reactions (≥2%) were pneumonia
(5%), febrile neutropenia (4.6%), pyrexia (3.3%), autoimmune
hemolytic anemia (2.9%), anemia (2.1%), and TLS (2.1%). b
• The most common adverse reactions (≥20%) of any grade were
neutropenia (45%), diarrhea (35%), nausea (33%), anemia (29%),
upper respiratory tract infection (22%), thrombocytopenia
(22%), and fatigue (21%). a
Drug Interactions
• For patients who have completed the ramp-up phase and are
on a steady daily dose of VENCLEXTA, reduce the dose by at
least 75% when used concomitantly with strong CYP3A
inhibitors. Resume the VENCLEXTA dose that was used prior to
initiating the CYP3A inhibitor 2 to 3 days after discontinuation
of the inhibitor.
• Avoid concomitant use of moderate CYP3A inhibitors or P-gp
inhibitors. If an inhibitor must be used, reduce the VENCLEXTA
dose by at least 50%. Monitor patients more closely for signs of
VENCLEXTA toxicities. Resume the VENCLEXTA dose that was
Please see Brief Summary of full Prescribing Information
on the following page.
Learn more at VENCLEXTA.com
80.2%
(n=85)
100
patients
HIGH
With VENCLEXTA monotherapy,
used prior to initiating the CYP3A inhibitor or P-gp 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.
• Avoid concomitant use of narrow therapeutic index P-gp
substrates. If these substrates must be used, they should be
taken 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 findings in animals, male fertility may be
compromised by treatment with VENCLEXTA.
a
b
VENCLEXTA [package insert]. North Chicago, IL: AbbVie Inc.
Data on file, AbbVie Inc.