The approval of Genentech and AbbVie’s Venclexta was based on Murano (NCT02005471), a randomized (1:1), multicenter, open-label trial of venetoclax with rituximab (VEN+R) versus bendamustine with rituximab (B+R) in 389 patients with CLL who had received at least one prior line of therapy. Patients in the VEN+R arm completed a 5-week ramp-up venetoclax scheduleand then received venetoclax 400 mg once daily for 24 months measured from the rituximab start date.
Rituximab was initiated after venetoclax ramp-up and given for 6 cycles (375 mg/m2 intravenously on cycle 1 day 1 and 500 mg/m2 intravenously on day 1 of cycles 2-6, with a 28-day cycle length). The comparator arm received 6 cycles of B+R (bendamustine 70 mg/m2 on days 1 and 2 of each 28-day cycle and rituximab at the above described dose and schedule).
Efficacy was based on progression-free survival (PFS) as assessed by an Independent Review Committee. After a median follow-up of 23 months, the median PFS was not reached in the VEN+R arm and was 18.1 months (95 percent CI: 15.8, 22.3) in the B+R arm (HR 0.19; 95 percent CI: 0.13, 0.28; p<0.0001). The overall response rate was 92 percent in the VEN+R arm compared to 72 percent for those treated with B+R.
In patients treated with VEN+R, the most common adverse reactions (incidence ≥20 percent) were neutropenia, diarrhea, upper respiratory tract infection, fatigue, cough, and nausea. Grade 3 or 4 neutropenia developed in 64 percent of these patients, and grade 4 neutropenia developed in 31 percent. Serious adverse reactions occurred in 46 percent of patients. Serious infections developed in 21 percent of patients, most commonly pneumonia (nine percent).
Due to rapid reduction in tumor volume, tumor lysis syndrome (TLS) is an important identified risk with venetoclax treatment. See the prescribing information for TLS risk stratification, prophylaxis, and monitoring.
FDA granted venetoclax in combination with rituximab Breakthrough Therapy Designation and granted this application priority review.
(Source: The U.S. Food and Drug Administration)