Venetoclax combined with rituximab is superior to bendamustine plus rituximab in patients with relapsed/refractory chronic lymphocytic leukemia – results from pre-planned interim analysis of the randomized phase-III-Murano-study.
In a phase-III-trial, treatment with the targeted cancer drug venetoclax in combination with rituximab more than doubled the likelihood that patients with chronic lymphocytic leukemia (CLL) would survive for two years without cancer progression compared to treatment with the standard chemo-immunotherapy drug bendamustine with rituximab The study is the first randomized trial to show venetoclax is superior to a standard chemo-immunotherapy regimen and the first randomized study to evaluate the survival benefit of venetoclax in combination with rituximab, according to researchers.
Venetoclax is approved for use against CLL in the United States and several other countries, but approvals are limited to small subgroups of patients, such as those with a specific genetic abnormality. The present trial, carried out at 109 sites globally, sought to assess the safety and efficacy of venetoclax in a broad patient population.
The trial enrolled 389 patients whose CLL had persisted or recurred after at least one previous course of treatment including chemotherapy. Half of the patients were randomly assigned to a regimen of six monthly doses of venetoclax plus rituximab and half received six cycles of bendamustine plus rituximab. Patients assigned to the venetoclax arm continued to use venetoclax alone for two years or until leukemia returned. To date, researchers have tracked patients for a median of about two years.
The vast majority (84,9%) of patients receiving venetoclax survived for two years without showing evidence of disease progression, compared to just 36,3% of those who received bendamustine. Venetoclax also outperformed bendamustine for the trial’s secondary endpoints, which included overall survival and markers of cancer remission. In particular, those on venetoclax were far more likely to achieve MRD clearance, which was achieved in 83,5% of those taking venetoclax and 23,1% of those taking bendamustine. These results suggest venetoclax could be discontinued after two years with a low risk of recurrence in those patients with a deep remission, researchers said.
„This is the first randomized trial comparing any of the new agents targeted to treat CLL against a standard chemoimmunotherapy program, and it has proved the superiority of the chemotherapy-free approach,“ said lead study author John Seymour, MBBS, PhD, director of the Haematology Department at the Peter MacCallum Cancer Centre and Royal Melbourne Hospital, Melbourne, Australia. „It suggests that venetoclax should replace chemotherapy for relapsed/refractory CLL and is suggestive that the combination with rituximab is the preferred manner to use the drug. There is also evidence of eradication of detectable disease that opens the prospect of time-limited therapy in this setting.“ While venetoclax was associated with a greater risk of abnormally low white blood cell counts, there was no increase in severe infections or deaths related to this side effect, said Seymour.
The researchers continue to monitor participants to assess long-term survival and disease progression.
ASH Annual Meeting 2017, abstract #LBA-2