The Food and Drug Administration (FDA) has approved Venclexta (venetoclax; AbbVie and Genentech), a B-cell lymphoma-2 inhibitor, in combination with Gazyva (obinutuzumab; Genentech), a CD20-directed cytolytic monoclonal antibody, for the treatment of patients with previously untreated chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).
The approval was based on data from the CLL14 trial, an open label, actively controlled, phase 3 study evaluating the efficacy and safety of venetoclax (administered for a fixed duration of 12 months) in combination with obinutuzumab (6 cycles) vs obinutuzumab in combination with chlorambucil in patients with previously untreated CLL with coexisting medical conditions (N=432). The primary efficacy outcome was progression-free survival (PFS).
Results showed that venetoclax in combination with obinutuzumab was associated with a significant reduction in the risk of disease worsening or death by 67% compared with obinutuzumab plus chlorambucil, with a median follow-up of 28 months (hazard ratio 0.33; 95% CI: 0.22-0.51; P <.0001). “The majority of patients receiving Venclexta in the trial remained progression-free at 2 years,” said Michael Severino, MD, vice chairman and president, AbbVie.
In addition, a higher rate of minimal residual disease (MRD)-negativity (defined as <1 CLL cell in 10,000 white blood cells) in the bone marrow and peripheral blood was noted with venetoclax plus obinutuzumab vs obinutuzumab plus chlorambucil (secondary endpoint).
With regard to safety, the most common adverse reactions associated with venetoclax given in combination with obinutuzumab were neutropenia, diarrhea, fatigue, nausea, anemia, and upper respiratory tract infection.
“The approval of the Venclexta combination means that patients with previously untreated CLL now have a finite duration, chemotherapy-free treatment option that can allow them to live longer without disease progression, induce high rates of minimal residual disease (MRD) negativity and, importantly, allow them to complete their course of therapy within 12 months,” said Michael Hallek, MD, lead investigator of the CLL14 study, Department of Internal Medicine and Center of Integrated Oncology at the University Hospital Cologne in Germany, and Head of the German CLL Study Group.
Venclexta is also indicated for CLL or SLL as monotherapy or in combination with rituximab, as well as for newly-diagnosed acute myeloid leukemia (AML) in adults ≥75yrs or who have comorbidities that preclude use of intensive induction chemotherapy, in combination with azacitidine, or decitabine, or low-dose cytarabine.
For more information visit venclexta.com.