A combination regimen consisting of Venclexta (venetoclax) and Gazyva (obinutuzumab) slowed disease progression in adults with chronic lymphocytic leukemia (CLL), according to recent company announcements.
CLL is the most common type of adult leukemia. Nearly 21,000 people will be diagnosed with CLL and about 4,500 will die from it this year, according to the American Cancer Society.
This type of leukemia involves overproduction of abnormal lymphocytes, usually antibody-producing B cells. As these abnormal cells grow out of control, they can crowd out normal blood cells, leading to anemia, increased susceptibility to infections and other complications.
CLL is difficult to cure. Although traditional chemotherapy can sometimes put leukemia into remission, it usually doesn’t eliminate all the cancer and relapse is common. Outcomes are better with targeted therapies that work directly against leukemia cells while sparing most healthy cells.
Venclexta interferes with the BCL-2 (B-cell lymphoma 2) regulatory protein, which interferes with the normal cell death cycle and allows cells to grow out of control. It is currently approved for CLL patients with or without chromosome 17p deletion—a genetic mutation associated with faster disease progression and poor treatment response—who have tried at least one other treatment.
Studies presented at last year’s American Society of Hematology (ASH) annual meeting showed that combining Venclexta with either Rituxan (rituxumab), a monoclonal antibody that targets the CD20 protein on B cells, or Imbruvica (ibrutinib), a BTK inhibitor that interferes with a signaling pathway that regulates B-cell growth, led to good outcomes.
Combining Venclexta with Gazyva also looks promising, according to press releases issued by AbbVie and Genentech, which are jointly developing the regimen. Gazyva is a newer CD20-directed antibody currently approved for CLL in combination with chemotherapy.
In a Phase III clinical trial known as CLL14, Venclexta plus Gazyva was pitted against Gazyva plus the chemotherapy drug chlorambucil in 445 CLL patients being treated for the first time. These participants had other health problems that made it difficult for them to use chemotherapy.
“People with chronic lymphocytic leukemia continue to need more treatment options because some patients are unable to tolerate chemotherapy regimens due to their underlying health,” said Sandra Horning, MD, Genentech’s chief medical officer.
After a year of treatment, Venclexta plus Gazyva demonstrated superior progression-free survival, meaning patients were still alive without worsening of disease, according to AbbVie and Genentech. Treatment was generally well tolerated, and the safety profile for the combination was consistent with the known side effects of each medicine when used alone.
The companies did not provide detailed study results, which they said would be presented at an upcoming conference—perhaps this year’s ASH meeting in December.
“Patients with chronic lymphocytic leukemia generally face a lifetime of continuous treatment to keep their disease from recurring or relapsing,” said AbbVie’s chief scientific officer Michael Severino, MD. “The positive results from the CLL14 trial further demonstrate the potential of venetoclax as a treatment with a fixed duration for patients with chronic lymphocytic leukemia and may serve as the basis to expand into first-line treatment.”
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Click here for full prescribing information for Venclexta.
Click here for full prescribing information for Gazyva.