Treatment of patients with relapsed or refractory chronic lymphocytic leukemia with a combination of Venclexta (venetoclax) plus Rituxan (rituximab) significantly extended the time a patient lived without signs of disease progression, compared to standard treatment, a new study shows.
The study, “Venetoclax–Rituximab in Relapsed or Refractory Chronic Lymphocytic Leukemia,” was published in the New England Journal of Medicine.
Over time, cancer cells can develop further mutations that make them resistant to standard treatment. This is often the case in patients with relapsed or refractory chronic lymphocytic leukemia. Therefore, additional treatments that target different aspects of tumor biology are necessary.
Chronic lymphocytic leukemia (CLL) cells have high levels of a protein called BCL2, which plays a role in blocking apoptosis, the pathway cells activate to undergo cell death. Researchers have suggested that targeting this gene could be a potential therapy.
Clinical trials have shown that Venclexta — an inhibitor of the protein BCL2 — is associated with a good response rate in patients with chronic lymphocytic leukemia who were previously treated with a different therapy. In 2016, the FDA approved Venclexta for CLL patients with a 17p deletion who have been treated with at least one prior therapy.
Rituxan is an established part of CLL therapy, and has been shown to work well in combination with Venclexta. The combination therapy is also known to help clear away any residual cancer cells that are left over after treatment.
Researchers conducted the Phase 3 MURANO trial (NCT02005471), which compared Venclexta in combination with Rituxan to a standard chemo-immunotherapy regimen — Treanda (bendamustine) in combination with Rituxan.
Results showed that progression-free survival was significantly higher in the Venclexta–Rituxan group compared to the patients on Treanda–Rituxan regimen. Out of the 194 patients in the Venclexta–Rituxan group, there were 32 events of progression or death compared to 114 events out of the 195 patients in the Treanda–Rituxan group.
Two years after entering the trial, 84.9% of patients in the Venclexta–Rituxan group were still alive and progression-free, compared to 36.3% in the Treanda–Rituxan group. Patients in the Venclexta–Rituxan group had a five times lower risk of progression or death compared to the Treanda–Rituxan group.
Interestingly, the benefit was seen across all subgroups of patients with relapsed or refractory chronic lymphocytic leukemia.
An independent review committee, whose members were unaware of the treatment-group assignments, assessed the outcomes of all the patients using clinical data, imaging, and bone marrow biopsies. The committee confirmed the benefit of Venclexta–Rituxan over Treanda–Rituxan.
Regarding adverse events, the rate of grade 3 or 4 neutropenia (low levels of neutrophils, a type of immune cell) was higher in the Venclexta–Rituxan group compared to the Treanda–Rituxan group. However, rates of grade 3 or 4 febrile neutropenia (neutropenia in combination with a fever) and infections or infestations were lower with Venclexta than with Treanda.
“Among patients with relapsed or refractory chronic lymphocytic leukemia, venetoclax in combination with rituximab resulted in a markedly higher rate of progression-free survival than standard bendamustine in combination with rituximab,” researchers concluded.