Currently Enrolling Trials
Venclexta (venetoclax) is a is a BCL-2 inhibitor. Rituxan (rituximab) is a CD20-directed cytolytic antibody.
Venclexta plus Rituxan is specifically indicated for the 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 is supplied as a tablet for oral administration. Rituxan is supplied as a solution for intravenous injection.
The recommended dosage of Venclexta is 400 mg once daily after completion of the 5-week ramp-up dosing schedule. Please see the drug label for the dosing schedule. Continue Venclexta until disease progression or unacceptable toxicity. Start rituximab administration after the patient has completed the 5-week ramp-up dosing schedule for Venclexta and has received Venclexta at the recommended dosage of 400 mg orally once daily for 7 days. Administer rituximab on Day 1 of each 28-day cycle for 6 cycles, at a dose of 375 mg/m2 intravenously for Cycle 1 and 500 mg/m2 intravenously for Cycles 2-6. Continue Venclexta 400 mg orally once daily for 24 months from Cycle 1 Day 1 of rituximab. Refer to the rituximab prescribing information for additional dosing information.
The FDA approval of the Venclexta plus Rituxan combination for CLL or SLL was based on MURANO, a Phase III open-label, international, multicenter, randomized study evaluating the efficacy and safety of Venclexta in combination with Rituxan compared to bendamustine in combination with Rituxan (BR). All treatments were of fixed duration. Following a five-week dose ramp-up schedule for Venclexta, patients on the Venclexta plus Rituxan arm received six cycles of Venclexta plus Rituxan followed by Venclexta monotherapy for up to two years total. Patients on the BR arm received six cycles of BR. The study included 389 patients with chronic lymphocytic leukemia (CLL) who had been previously treated with at least one line of therapy. Patients were randomly assigned in a 1:1 ratio to receive either Venclexta plus Rituxan or BR. The primary endpoint of the study was progression-free survival (PFS). The results showed that a fixed duration of treatment with Venclexta plus Rituxan significantly reduced the risk of disease progression or death (PFS) by 81 percent compared with bendamustine plus Rituxan, a current standard of care.
Adverse effects associated with the use of Venclexta plus Rituxan may include, but are not limited to, the following:
- low white blood cell count
- upper respiratory tract infection
Mechanism of Action
Venclexta (venetoclax) is a selective and orally bioavailable small-molecule inhibitor of BCL-2, an antiapoptotic protein. Overexpression of BCL-2 has been demonstrated in CLL and AML cells where it mediates tumor cell survival and has been associated with resistance to chemotherapeutics. Venetoclax helps restore the process of apoptosis by binding directly to the BCL-2 protein, displacing pro-apoptotic proteins like BIM, triggering mitochondrial outer membrane permeabilization and the activation of caspases.
Rituxan (rituximab) is a monoclonal antibody that targets the CD20 antigen expressed on the surface of pre-B and mature B-lymphocytes. Upon binding to CD20, rituximab mediates B-cell lysis. Possible mechanisms of cell lysis include complement dependent cytotoxicity (CDC) and antibody dependent cell mediated cytotoxicity (ADCC). B cells are believed to play a role in the pathogenesis of rheumatoid arthritis (RA) and associated chronic synovitis. In this setting, B cells may be acting at multiple sites in the autoimmune/inflammatory process, including through production of rheumatoid factor (RF) and other autoantibodies, antigen presentation, T-cell activation, and/or proinflammatory cytokine production.
For additional information regarding the use of Venclexta plus Rituxan in treating CLL or SLL, please visit the Venclexta website.