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.