Study parameters

• Based on results from CLL14: a randomized (1:1), multicentre, open-label Phase 3 study that evaluated the efficacy and safety of VENCLEXTA in combination with obinutuzumab versus obinutuzumab in combination with chlorambucil for previously untreated CLL in patients with coexisting medical conditions (total CIRS score >6 or CrCl <70 mL/min). Patients in the study were assessed for risk of tumour lysis syndrome (TLS) and received prophylaxis accordingly prior to obinutuzumab administration. All patients received obinutuzumab at 1000 mg on Cycle 1 Day 1 (the first dose could be split as 100 and 900 mg on Days 1 and 2), and 1000 mg doses on Days 8 and 15 of Cycle 1, and on Day 1 of each subsequent cycle, for a total of 6 cycles. On Day 22 of Cycle 1, patients in the VENCLEXTA + obinutuzumab arm began the 5-week VENCLEXTA ramp-up schedule. After completing the ramp-up schedule on Cycle 2 Day 28, patients received VENCLEXTA 400 mg once daily from Cycle 3 Day 1 until the last day of Cycle 12 as a finite treatment duration. Following completion of 12 months of VENCLEXTA, patients stopped therapy and were continued to be followed for disease progression and overall survival. Patients randomized to the obinutuzumab + chlorambucil arm received 0.5 mg/kg oral chlorambucil on Day 1 and Day 15 of Cycles 1 to 12, in the absence of disease progression or unacceptable toxicity. Each cycle was 28 days.

• Based on results from MURANO: a randomized (1:1), multicentre, open-label Phase 3 study with time-limited therapy that evaluated the efficacy and safety of VENCLEXTA in combination with rituximab versus bendamustine in combination with rituximab in patients with R/R CLL who had received at least one line of prior therapy. Patients previously treated with VENCLEXTA were excluded. Patients in the VENCLEXTA + rituximab arm completed the 5-week ramp-up schedule of VENCLEXTA and received 400 mg VENCLEXTA daily for 24 months from Day 1, Cycle 1 of rituximab in the absence of disease progression or unacceptable toxicity. After the 5-week dose ramp-up, rituximab was initiated at 375 mg/m² for Cycle 1 and 500 mg/m² for Cycles 2–6. Each cycle was 28 days. Patients randomized to bendamustine + rituximab received bendamustine at 70 mg/m² on Days 1 and 2 for 6 cycles and rituximab at the above described dose and schedule. Following completion of the 24-month treatment in the VENCLEXTA + rituximab arm or 6 cycles of bendamustine + rituximab, patients continued to be followed for disease progression and overall survival. A total of 389 patients were randomized; 194 to the VENCLEXTA + rituximab arm and 195 to the bendamustine + rituximab arm.