Trials confirm patients with chronic lymphocytic leukemia treated with venetoclax-based regimens achieve higher rates of undetectable minimal residual disease, which may be associated with a lower risk of future disease progression or death.
New data from a pair of pivotal phase 3 studies support the efficacy of fixed-duration, chemotherapy-free, venetoclax (Venclexta; Genentech and AbbVie)-based combinations in certain people with chronic lymphocytic leukemia (CLL). These studies also provide more evidence on the potential value of minimal residual disease (MRD), according to Genentech.
Venetoclax is a targeted, prescription medicine designed to selectively bind and inhibit the B-cell lymphoma-2 (BCL-2) protein. Data from the pair of phase 3 trials were presented during the virtual 62nd American Society of Hematology Annual Meeting and Exposition.
CLL is the most common type of adult leukemia, with an estimated number of more than 20,000 new cases in the United States diagnosed in 2020. The disease is considered incurable and many people require additional treatment because cancerous cells return.
Five-year data from the MURANO (NCT02005471) trial continue to show sustained investigator-assessed progression-free survival (PFS) with venetoclax plus rituximab (Rituxan). The open-label, international, multicenter, randomized study included 389 patients with CLL, with or without 17p deletion, who had been previously treated with at least 1 line of therapy.
According to Genetech’s oral presentation, results of the trial showed as follows:
According to Genentech, data from the CLL14 (NCT02242942) study contributes to growing evidence regarding the potential of MRD measurements to predict future outcomes for certain people with previously untreated CLL who were treated with fixed-duration venetoclax plus obinutuzumab (Gazyva). In this study, 432 patients with previously untreated CLL were randomly assigned to receive either a 12-month duration of venetoclax with 6-month duration of obinutuzumab, or 6-month duration of obinutuzumab with 12-month duration of chlorambucil:
According to Genentech, venetoclax can cause serious adverse effects (AEs) such as tumor lysis syndrome (TLS). In turn, TLS may cause kidney failure. Neutropenia and infections are other potential serious AEs.
The most common AEs of using venetoclax in combination with obinutuzumab or rituximab, or alone in people with CLL or SLL include low white blood cell count, low platelet count, low red blood cell count, diarrhea, nausea, upper respiratory tract infection, cough, muscle and joint pain, tiredness, and swelling of arms, legs, hands, and feet.
The most common AEs of using venetoclax in combination with azacitidine or decitabine or low-dose cytarabine in people with AML include nausea, diarrhea, low platelet count, constipation, low white blood cell count, fever with low white blood cell count, tiredness, vomiting; swelling of arms, legs, hands, or feet; fever, lung infection, shortness of breath, bleeding, low red blood cell count, rash, abdominal pain, infection in the blood, muscle and joint pain, dizziness, cough, sore throat, and low blood pressure.
Genentech is continuing to investigate venetoclax in a robust clinical development program. This includes the phase 3 CRISTALLO (NCT04285567) trial in previously untreated CLL, which uses MRD as a primary endpoint.