FDA Approves Treatment for Chronic Lymphocytic Leukemia & Small Lymphocytic Lymphoma

Today, VENCLEXTA, AbbVie Inc, and Genentech Inc announced that the US food and Drug Administration has approved venetoclax for treatment of patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), with or without 17p deletion, who have received at least one prior therapy.

"VENCLEXTA now gives indicated patients a new opportunity to significantly reduce the risk of their disease progressing, compared to a current standard of care. This combination provides previously treated CLL or SLL patients with a chemotherapy-free, fixed duration treatment allowing patients the ability to stop treatment after approximately two years,” stated Michael Severino, MD, executive vice president, research and development, and chief scientific officer, AbbVie, exclusively to Rare Disease Report®.

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 were administered at least 1 prior line of therapy, served as the basis for approval. Measured from the rituximab start date, participating subjects in the VEN+R arm completed a 5-week ramp-up venetoclax schedule and were then administered venetoclax 400 mg once daily for 24 months.

After venetoclax ramp-up, rituximab was initiated and administered 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). Six 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) were administered to the comparator arm.

Progression-free survival (PFS), as assessed by an Independent Review Committee, served as the basis for efficacy. The median PFS was not reached in the VEN+R arm and was 18.1 months (95% CI: 15.8, 22.3) in the B+R arm (HR 0.19; 95% CI: 0.13, 0.28; p<0.0001) as assessed post a median follow-up of 23 months. The overall response rate in the VEN+R arm was 92% while those treated with B+R experienced an overall response rate of 72%.

The most common adverse reactions (incidence ≥20%) in patients treated with VEN+R included neutropenia, diarrhea, upper respiratory tract infection, fatigue, cough, and nausea. In addition, 64% of these patients developed Grade 3 or 4 neutropenia, and 31% developed grade 4 neutropenia. Forty-six percent of patients experienced serious adverse reactions, and 21% of patients developed serious infections with the most common being pneumonia (9%).

Important identified risks with venetoclax include tumor lysis syndrome (TLS) due to rapid reduction in tumor volume.

A 5-week ramp-up will commence all approved venetoclax regimens.